Implantable pressure transducer system optimized for reduced thrombosis effect

ABSTRACT

This invention relates generally to systems and methods for optimizing the performance and minimizing complications related to implanted sensors, such as pressure sensors, for the purposes of detecting, diagnosing and treating cardiovascular disease in a medical patient. Systems and methods for anchoring implanted sensors to various body structures are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority under 35 U.S.C. §119(e) to U.S.Provisional Application No. 60/564,315 filed on Apr. 22, 2004, and isalso a continuation-in-part of co-pending U.S. application Ser. No.10/672,443 filed on Sep. 26, 2003, which claims priority under 35 U.S.C.§119(e) to U.S. Provisional Application No. 60/413,758 filed on Sep. 26,2002, the disclosures of which are incorporated by reference herein intheir entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to systems and methods for optimizingthe performance and minimizing complications related to implantedsensors, such as pressure sensors, for the purposes of detecting,diagnosing and treating cardiovascular disease in a medical patient.

2. Description of the Related Art

There are approximately 60 million people in the U.S. with risk factorsfor developing chronic cardiovascular diseases, including high bloodpressure, diabetes, coronary artery disease, valvular heart disease,congenital heart disease, cardiomyopathy, and other disorders. Another10 million patients have already suffered quantifiable structural heartdamage but are presently asymptomatic. Still yet, there are about 5million patients with symptoms relating to underlying heart damagedefining a clinical condition known as congestive heart failure (CHF).Although survival rates have improved, the mortality associated with CHFremains worse than many common cancers. The number of CHF patients isexpected to grow to 10 million within the coming decade as thepopulation ages and more people with damaged hearts survive.

CHF is a condition in which a patient's heart works less efficientlythan it should, and a condition in which the heart fails to supply thebody sufficiently with the oxygen-rich blood it requires, either duringexercise or at rest. To compensate for this condition and to maintainblood flow (cardiac output), the body retains sodium and water such thatthere is a build-up of fluid hydrostatic pressure in the pulmonary veinsthat drain the lungs, which is generally equivalent to the left atrialpressure. As hydrostatic pressure exceeds oncotic pressure and lymphflow, fluid transudates from the pulmonary veins into the pulmonaryinterstitial spaces, and eventually into the alveolar air spaces. Thiscomplication of CHF is called pulmonary edema, which can cause shortnessof breath, hypoxemia, acidosis, respiratory arrest, and death. AlthoughCHF is a chronic condition, the disease often requires acute hospitalcare. Patients are commonly admitted for acute pulmonary congestionaccompanied by serious or severe shortness of breath.

One relatively new approach for treating cardiovascular disease is toimplant sensors, such as pressure sensors in various chambers of theheart or adjacent vasculature such as the pulmonary arteries or veins,for the purposes of detecting early cardiac decompensation andprevention of pulmonary congestion and edema. Another potentialadvantage of implanted pressure transducers is that they may be usefulin preventing overtreatment with resultant hypoperfusion of vital organssuch as the kidneys. Such an approach utilizing a left atrial pressuretransducer coupled with a medical therapy optimization system isdescribed by Eigler et al. in U.S. Pat. No. 6,328,699, hereinincorporated by reference.

One particular type and method of sensor placement is known astransmural placement where the sensor device enters the desired locationby perforation of the tissue wall separating the outside the structureto inside the structure. Generally the sensor device resides on bothsides and within a wall separating parts of the body, parts of an organsuch as the heart, or separating a body structure form the rest of thebody (the wall of a blood vessel). Sensor packages can be transmurallyplaced in the left atrium of the heart by a minimally invasivepercutaneous catheter based procedure known as transseptalcatheterization as originally described by Ross (Ross, J., Jr.:Transseptal left heart catheterization: A new method of left atrialpuncture. Ann. Surg. 1949:395, 1959) and Cope in 1959 (Cope, C.:Technique for transseptal catheterization of the left atrium:Preliminary report. J. Thorac. Surg. 37:482, 1959), and modified byBrockenbrough and Braunwald in 1960 (Brockenbrough E C, Braunwald E: Anew technique for left ventricular angiocardiography and transseptalleft heart catheterization. Am J Cardiol 6:1062, 1960) and subsequentlyby Ross in 1966 (Ross J Jr.: Considerations regarding the technique fortransseptal left heart catheterization. Circulation 34:391, 1966), allherein incorporated by reference. More invasive surgical procedures cantransmurally place sensor devices in any cardiac chamber or blood vesselof sufficient size including the pulmonary arteries and veins.

Implantable pressure transducers are known in the art. For example, U.S.Pat. Nos. 4,023,562, 4,407,296, 4,407,296, 4,485,813, 4,432,372,4,774,950, 4,899,751, 4,899,752, 4,986,270, 5,027,816, 4,353,800,4,846,191, and 6,379,308 describe various types of pressure sensors.However, pressure sensors that are currently described in the art arenot suitable for chronic implantation in the body for several reasons.For example, some pressure transducers are not hermetically sealed, orotherwise properly protected, and thus susceptible to degradation bybodily fluids. Other transducers are constructed such that theirspecific geometries or components cause thrombus formation, apotentially life threatening condition. Several transducers areconstructed in a manner that result in significant “drift” of thepressure sensor, either due to tissue overgrowth or some othermechanism, thus resulting in inaccurate pressure measurements, which inmany cases cannot be properly or easily recalibrated. Thus, there stillremains a need in the art for an implantable sensor, such as a pressuretransducer, that is stable, safe, effective, accurate, and, if needed,easily recalibrated.

SUMMARY OF THE INVENTION

This invention relates generally to systems and methods for optimizingthe performance and minimizing complications related to implantedsensors, such as pressure sensors, for the purposes of detecting,diagnosing and treating cardiovascular disease in a medical patient.Systems and methods for anchoring implanted sensors to various bodystructures are also provided.

Several embodiments of the present invention relate generally toimplantable physiological sensors. In one embodiment, a pressure sensor,or pressure transducer, that is suitable for chronic implantation in thebody is provided. In another embodiment, a pressure transducer systemthat exhibits long-term stability following chronic implantation in thecardiovascular system is provided. In one embodiment, the pressuretransducer remains stable despite the biological reactions that thesesystems induce. The sensors and methods described in some of theembodiments facilitate optimal healing and subsequent stability oftransmurally implanted pressure sensors. Several embodiments of thecurrent invention are particularly advantageous because they reduce therisk of thrombus formation and are not as susceptible to tissueovergrowth that causes drift of the pressure sensor. Other embodimentsof the invention are designed to optimize performance. In oneembodiment, deployment devices, anchoring means and/or retrieval toolsare provided in conjunction with the sensor. In another embodiment, thesensor is at least partially enclosed in protective packaging. Inanother embodiment, the sensor is designed to minimize viscoelasticdrift. In yet another embodiment, temperature compensation is provided.In a further embodiment, the effects of output artifacts, or sideloading, are minimized.

In some embodiments, the implantable pressure sensing system, comprisesone or more sensing interfaces. The phrase “sensing interface” as usedherein shall be given its ordinary meaning and shall also include one ormore materials or structures that protects a sensor from direct exposureto the environment (e.g., blood, tissue, etc.) while still preservingthe sensor's sensing function. Sensing interfaces include, but are notlimited to, diaphragms, hydrogels, metallic foils, plastics, membranesand other materials. In several embodiments, at least a portion of thesensing interface is configured to minimize thrombosis. As used hereinthe phrase “reduce thrombosis” shall be given its ordinary meaning andshall also include the partial prevention, reduction, hindrance ordestruction of a blood clot or thrombus by, for example: (1)pharmacological agents that affect clot or thrombus formation, growth,or dissolution; (2) the promotion of neoendothelial overgrowth by, forexample, providing growth channels or biological agents that facilitatetissue growth; and/or (3) comprising a thrombosis resistant coating or acoating that reduces platelet (or other blood component) activation oraggregation. In one embodiment, an implantable pressure sensing systemis provided, comprising a pressure sensor assembly, said pressure sensorassembly comprising a sensing interface having a first face and a secondface and at least one pressure sensing unit comprising a sensing surfaceand non-sensing surface, wherein said pressure sensing unit contactssaid second face of said sensing interface, and a sensor housing,wherein said sensor housing is hermetically sealed to said pressuresensor assembly, wherein at least portion of said sensing interface isadapted to reduce thrombosis. In some embodiments, said sensinginterface of the pressure sensor assembly comprises a diaphragm. In someembodiments, at least one said pressure sensing unit comprises a straingauge. In one embodiment, said sensing interface and said pressuresensing unit are integrally formed in a micro electromechanical systemsdevice. Said diaphragm may comprise a plurality of grooves to facilitatetissue ingrowth. At least a portion of said diaphragm may have abiocompatible coating. Said biocompatible coating may be bio-stable orbio-erodable. Said biocompatible coating may be resistant to thrombusformation, capable of controlling tissue ingrowth, configured to reduceformation of fibrous tissue or not reduce growth of endothelial tissue.In some embodiments, at least a portion of said sensor housing isconfigured to resist transmission of side-load forces to said sensinginterface under physiologic conditions. Said sensor housing may comprisea side-loading force absorbing structure about the sensing interface. Insome embodiments, at least a portion of said sensor housing has apolished surface and/or a thrombosis-resistant coating. In oneembodiment, said sensor housing comprises one or more materials selectedfrom the group consisting of nitinol, stainless steel alloys, titaniumalloys, cobalt chromium, tantalum, a ceramic, a glass or combinationthereof. In some embodiments, the invention further comprising adrug-eluting component. Said drug-eluting component may comprise aplurality of reservoirs on the surface of said sensor housing withdepots of one or more releasable treatment agents. Said drug-elutingcomponent may further comprise a drug for controlling neointimalthickness. In some embodiments, said diaphragm is configured to resistthe inhibition of diaphragm motion by overlying tissue overgrowth. Insome embodiments, said diaphragm has a compliance substantially lowerthan the compliance of physiological levels of overlying tissueovergrowth. In one embodiment, said diaphragm has an average thicknesssufficient to provide a compliance substantially lower than thecompliance of physiological levels of overlying tissue overgrowth whilecapable of a displacement sufficient for said strain gauges to generatea usable sensor signal over a physiological range of blood pressures. Inone embodiment, said diaphragm has a diameter of about 2.5 mm and anaverage thickness of about 25 microns to about 76 microns. In anotherembodiment, said diaphragm has a diameter of about 2.5 mm and an averagethickness of about 76 microns to about 127 microns. In still anotherembodiment, said diaphragm has a diameter of about 2.5 mm, an averagethickness of about 50 microns, and a displacement of about 4 nm at aboutthe center of said diaphragm. In one embodiment, said diaphragm has acompliance of about 10,000 times less or lower than the compliance ofphysiological levels of overlying tissue overgrowth. In anotherembodiment, said diaphragm has a compliance of about 100,000 times lessor lower than the compliance of physiological levels of overlying tissueovergrowth. In one embodiment, said first face and said second face ofsaid diaphragm are generally flat to enhance diaphragm displacementcapability. Said diaphragm may comprise a material selected from a groupconsisting of titanium or Ti 4-6. In some embodiments, the sensorhousing further comprising a filling material within the sensor housing.In some embodiments, the filling material is selected from one or moreof the group comprising helium, argon or other noble gas, an electricalinsulating liquid, or a moisture absorbent material.

In one embodiment, an implantable pressure sensing system is provided,comprising a pressure transducer assembly comprising a microelectromechanical systems pressure transducer; said pressure transducerhaving a first face with a sensing surface and a non-sensing surface,and a second face having a connection area and a non-connection area, asensor housing, wherein said sensor housing is hermetically sealed tosaid pressure transducer assembly, wherein said sensing surface of thepressure transducer is configured to reduce thrombosis. Said sensorhousing may be hermetically sealed to said pressure transducer assemblyat the non-sensing surface of said first face. In other embodiments,said sensor housing is hermetically sealed to said pressure transducerassembly at the non-connection area of said second face. In oneembodiment, said sensor housing is hermetically sealed to said pressuretransducer assembly with a gold-silicon bonding layer.

In one embodiment, a device for monitoring a patient is provided,comprising a means for sensing a physiological parameter, an implantablemeans for housing the sensing means, a means for interfacing the sensingmeans with the patient environment, and a means for reducing thrombosison the interfacing means.

In one embodiment, an implantable pressure sensing system is provided,comprising a pressure transducer assembly comprising a microelectromechanical systems pressure transducer; said pressure transducerhaving a first face with a sensing surface and a non-sensing surface, asecond face having a connection area and a non-connection area, and asensor housing, wherein said sensor housing is hermetically sealed tosaid pressure transducer assembly. Said sensor housing may behermetically sealed to said pressure transducer assembly at thenon-sensing surface of said first face, or at the non-connection area ofsaid second face. In some embodiments, said sensor housing ishermetically sealed to said pressure transducer assembly with agold-silicon bonding layer.

In one embodiment, an implantable sensing system is provided, comprisinga biocompatible sensor housing, a pressure sensing interfacehermetically sealed to the sensor housing, and a plurality of straingauges joined to the pressure interface, wherein the plurality ofpressure sensors are arranged in a Wheatstone bridge configuration. Insome embodiments, at least one said pressure sensors comprises a siliconstrain gauge. Said silicon strain gauge may further comprise aninsulation layer. In a further embodiment, said insulation layercomprises silicon dioxide grown on the bottom of said silicon straingauge. In some embodiments, the plurality of pressure sensors comprisesan inner set of strain gauges and an outer set of strain gauges, whereinsaid inner set is generally located about the center of said second faceof said sensing interface and said outer set is generally located nearthe periphery of said second face of said sensing interface. In someembodiments, said inner set of strain gauges and said outer set ofstrain gauges may be generally oriented orthogonally on said second faceof said sensing interface, or may be generally oriented about 180degrees apart on said second face of said sensing interface. Someembodiments of the invention further comprise a temperature compensationsystem. Said temperature compensation system may comprise a temperaturesensing element capable of providing temperature-related informationover a physiological range of temperatures. Said temperaturecompensation system may be a temperature compensating arrangementintegral with said plurality of strain gauges, wherein said plurality ofstrain gauges are resistive strain gauges arranged in a Wheatstonebridge configuration. In one embodiment, at least one strain gauge has afrequency response from about 500 Hz to about 2000 Hz. In otherembodiments, at least one strain gauge has a frequency response lessthan about 500 Hz. In one embodiment, at least one strain gauge has afrequency response greater than about 2000 Hz. The invention may furthercomprise at least one semiconductor component configured to at least onefunction selected from the group comprising: power control, pressuresignal transduction, local signal processing and data telemetry.

In one embodiment, an implantable pressure sensor is provided,comprising a means for pressure sensing in the body, a means for housingsaid sensing means chronically in a body, and a means for providingtemperature correction for the pressure sensing means.

In one embodiment, a method for monitoring a patient is provided,comprising, providing a hermetically sealed pressure transducer in abody, detecting a pressure signal with the hermetically sealed pressuretransducer; and modulating the pressure signal with atemperature-related signal. In some embodiments, the temperature-relatedsignal originates from a temperature sensor. In some embodiments, thetemperature-related signal originate from a plurality of resistivestrain gauges in a Wheatstone bridge configuration.

In one embodiment, a physiological lead system is provided, comprisingan elongate member having a proximal end and a distal end, a lead systemlocated generally at the distal end of said elongate member; and adistal anchor assembly engaged to said elongate member, said distalanchor assembly comprising at least one protruding member with at leastone tissue ingrowth path. In some embodiments, at least one said tissueingrowth path comprises a straight, fixed-width slit. In one embodiment,at least one said tissue ingrowth path comprises a hole in saidprotruding member. In one embodiment, said protruding member comprises aplurality of holes of similar diameters. In one embodiment, saidprotruding member comprises a plurality of holes of different diameters.In one embodiment, at least one said tissue ingrowth path comprises acurved slit. In one embodiment, at least one said tissue ingrowth pathcomprises a variable width slit. In one embodiment, at least one saidtissue ingrowth path comprises a groove. In one embodiment, at least onesaid protruding member has a curved or angled configuration. In someembodiments, the curved or angled configuration of said protrudingmember lies in the same plane as the longitudinal axis of said elongatemember. In another embodiment, the curved or angled configuration ofsaid protruding member lies in the same plane as a perpendicular radialcross section of said elongate member.

The physiological lead system of claim 60, wherein said distal anchorassembly is engaged to said elongate member at a separation distancefrom said lead system such that said lead system is substantiallyunaffected by forces acting said distal anchor assembly.

The physiological lead system of claim 60, further comprising a proximalanchor assembly engaged to said elongate member generally between saiddistal anchor assembly and the proximal end of said elongate member. Inone embodiment, at least a portion of said distal anchor assembly has abiocompatible coating. In one embodiment, at least a portion of one saidtissue ingrowth path has a biocompatible coating. In one embodiment, theinvention further comprises a drug-eluting system. In a furtherembodiment, said drug-eluting system comprises a coating on said distalanchor assembly. The drug-eluting coating may be configured for aparticular elution rate or elution duration. Said drug-eluting systemmay further comprise a drug for controlling neointimal thickness. Insome embodiments, at least a portion of said distal anchor assembly hasa biocompatible coating. Said biocompatible coating may be bio-stable orbio-erodable. Said biocompatible coating may be resistant thrombusformation, capable of controlling tissue ingrowth, resistant tocorrosion, capable of reducing formation of fibrous tissue, and/orconfigured not prevent growth of endothelial tissue. In one embodiment,said biocompatible coating comprises a corticosteroid. In oneembodiment, said biocompatible coating comprises parylene. Said elongatemember may further comprise a removable stylet and a stylet lumen.

In one embodiment, a sensor is designed to minimize viscoelastic drift.The thickness of epoxy adhesive attaching strain gauges to diaphragm maybe minimized by growing a silicon dioxide or other insulating layer onthe bottom of the silicon strain gauges or the metallic diaphragm, sothat adhesive does not also have to serve as an insulating layer.

In one embodiment, viscoelastic drift is calibrated, predicted, andcorrected. In one embodiment, viscoelastic properties of the pressuretransducer are characterized during pre-implant calibration. In oneembodiment, known viscoelastic properties are used in combination withthe recorded pressure variations over time to obtain pressuremeasurements that are corrected for viscoelastic drift. In oneembodiment, a software algorithm is used to automatically correct forviscoelastic drift due to varying average pressure.

In one embodiment, effects of side loading on the sensor are minimized.In one embodiment, at least a portion of the casing adjacent to thediaphragm is made substantially inflexible and non-distortable such thatthe diaphragm is not distorted by side-load forces under physiologicconditions. In one embodiment, a fixation anchor attachment to thehousing is located as far as possible from the portion of the housingthat supports the diaphragm, so that forces exerted by the anchor legscause less distortion of the diaphragm. In one embodiment, strain gaugesare oriented 90° from each other rather than the standard 180°orientation, and connected in a Wheatstone bridge configuration suchthat differential resistance changes between the strain gaugessubstantially cancel, while common-mode changes in resistance areadditive. Any feature mentioned above may be used in combination withothers.

In one embodiment, thrombogenicity of the sensor is minimized bypolishing, including electropolishing, coating, including parylene, asmall surface area, a low profile, a profile configured to reduce flowdisruption and/or encouraging rapid tissue overgrowth/ingrowth.

In one embodiment, materials that promote rapid tissue coverage, healwithout chronic inflammation, and develop a thin covering of neointimaare provided. These may include alloys of stainless steel, Nitinol,titanium alloys, cobalt chromium and/or tantalum.

In one embodiment, pressure artifacts due to atrial wall stresses areminimized by providing features on the sensor housing that reduce thecoupling of these stresses to the sensor diaphragm. In one embodiment,the sensor housing comprises grooves, threads, or tabs generally aroundits distal circumference to anchor tissue overgrowth, reducing thecoupling of stress within the tissue to the sensor diaphragm. In oneembodiment, the sensor housing comprises a cylindrical rim that extendsdistally beyond and surrounding the sensor diaphragm, providing abarrier protecting the diaphragm from the transmission of tissuestresses.

In another embodiment, coupling of wall stresses is minimized byproviding for drug delivery from a ring or band about the distalcircumference of the sensor housing. The drug may include anantiproliferative agent such as paclitaxel or sirolimus, as is known inthe field of drug eluting stents to prevent restenosis. Other bioactivedrugs to reduce proliferation, thrombosis or inflammation, as are knownto those skilled in the medical arts may also be used. In oneembodiment, a source of ionizing radiation is provided in a band aroundthe distal circumference of the sensor. It is known by those skilled inthe art that ionizing radiation reduces or prevents tissue proliferationfollowing tissue injury. In one embodiment, the sensor diaphragmcomprises a radioactive source such as Phosphorus-32 or Strontium-90,which are known to emit beta particles that can reduce tissueproliferation.

In one embodiment, improved sensor reliability and accuracy is provided.

In one embodiment, improved sensor positioning stability is provided.

In one embodiment, elution of one or more drugs to reduce neointimalthickness is provided.

In one embodiment, slow release of low doses over longer periods isprovided.

In one embodiment, slots, grooves, or holes in distal anchor legs tominimize path lengths for tissue ingrowth are provided.

In one embodiment, an implantable pressure monitor is provided, saidmonitor comprising distal anchors, said anchors comprising one or morelegs, said legs configured with one or more slots for the purpose toadvantageously promote more rapid tissue overgrowth in a deployedposition, which will advantageously aid in securement of the device tothe septum wall and prevent thrombus formation. In another embodiment,the slots in the legs can vary in width. In another embodiment, theslots in the legs can be curved or serpentine. In another embodiment,the slots in the legs may be replaced by one or more holes of equal ordiverse diameters. In yet another embodiment, the legs can be keyed orslotted at right angles to their long axes from one or both sides.

In one embodiment, surface grooves are formed on the diaphragm topromote rapid tissue ingrowth. The shape of groove long axis may belinear, serpentine, circumferential or any other beneficial grooveshape. The cross-sectional shape of groove may be rectangular,triangular (“Vee”), semi-round or any other beneficial shape. Thegrooves may be filled with or coated by bio-stable or bio-erodablepolymer or other coating agents, including one or more drugs thatcontrol tissue growth rate or thrombus formation

In one embodiment, biocompatible coatings such as parylene are provided.Such coatings may minimize platelet adhesion and aggregation, provideelectrical insulation (for pacing) and/or prevent corrosion of metalliccomponents.

In one embodiment, the invention comprises a coating on the diaphragmsurface and/or on anchor surfaces that inhibits or minimizes theformation of undesirable fibrous tissue, while not preventing thebeneficial growth of an endothelial covering.

In one embodiment, a plurality of small indentations or holes in thedevice or anchor surfaces are provided to serve as depots for controlledrelease of antiproliferative substances

In one embodiment the invention, a pressure transducer is provided thatis designed so that calibration parameters are minimally affected bytissue overgrowth, and may include a very low compliance diaphragmcompared with tissue overgrowth, and/or diaphragm thickness maximized tominimize compliance, consistent with sufficient compliance to deriveadequate transducer signal. In one embodiment, the 2.5 mm diameterdiaphragm is between about 0.001 to 0.003 inches (25 to 76 microns)thick. In another embodiment, the diaphragm thickness is between about0.003 to 0.005 inches (76 to 127 microns). In one embodiment, a 2.5 mmdiameter by 50-micron thick titanium foil diaphragm has a displacementat its center of only about 4 nm per mm Hg pressure change. In oneembodiment, a pressure transducer diaphragm constructed of Ti 6-4 withmaterial properties comprising of approximately R_(o)=1.1 mm, v=0.31,t=0.05 mm, and E=100 GPa is provided. In another embodiment, a lowcompliance pressure transducer is fabricated from, for example, silicon,using micro electromechanical systems (MEMS) techniques. In oneembodiment, a diaphragm is manufactured to maximize flatness, whichmaximizes gain for a given diaphragm thickness, is provided.

In one embodiment, a pressure sensor includes temperature compensationso that pressure measurements will be minimally affected by temperaturechange is provided. In one embodiment, an apparatus to measuretemperature at the site of the sensor is provided. In one embodiment,the temperature compensation or modulation is achieved by using multipleresistive strain gauges arranged in a Wheatstone bridge, such that theelectrical voltage output of the bridge is proportional to the ratio oftwo or more resistances, all of which depend on temperature in a similarway, thus reducing the affect of temperature on the pressure reading. Itcan also be achieved by selecting resistive strain gauges withessentially identical temperature coefficients, and connecting thestrain gauges in a Wheatstone bridge configuration.

In one embodiment, an internal thermometer that is independent ofpressure is provided where prior to implantation calibrating thetemperature coefficient of the pressure reading based on this measuredtemperature. After implantation the measured temperature is used toselect the appropriate pressure calibration coefficients. In oneembodiment, a band-gap voltage reference is used to create a currentproportional to absolute temperature that is then compared to thetemperature-independent voltage reference, thereby deriving a measure oftemperature.

In one embodiment, the device can be easily recalibrated usingnon-invasive method, such as a Valsalva maneuver and/or offsetcalibration, where the gain is not affected by tissue.

In one embodiment, complete encasement of system within hermetic housingis provided to protect against the damaging effects of bodily fluids.The sensor may be enclosed in metal packaging. Environmental pressuremay be coupled to sensor through a diaphragm bonded to the metalhousing.

In one embodiment, a delivery catheter permits simultaneous measurementof fluid pressure from the catheter tip during transducer packagetransit and deployment. The delivery catheter is configured to besufficiently large in diameter to allow the catheter to be filled with acontinuous cylindrical column of fluid surrounding the sensor module andits lead. The delivery catheter permits injection of radiographiccontrast material with the transducer system in its lumen to localizepositioning during transducer system deployment. Positioning can bedetermined under fluoroscopy by contrast injection and pressuremeasurement thought side arm port the delivery catheter. In oneembodiment, after the distal anchor legs expand to assume their expandedstate on a distal side of the septum wall, contrast material is injectedto assure correct positioning in the left atrium. The catheter isfurther retracted while holding the stylet and sensor assembly in placeuntil the distal edge of the catheter is coincident with the proximalend of the sensor assemble, which can be verified by visualizing thealignment of the radiopaque markers on the sensor assembly and thedelivery catheter under fluoroscopy. Further contrast is injected whilethe entire catheter, stylet and sensor assembly are retracted in 1 to 2mm increments until contrast material is fluoroscopically observedexiting the tip of the catheter into the right atrium. At this pointfurther retraction of the catheter will expose the proximal anchor,allowing it to relax to its expanded state on a proximal side of theseptum wall.

In one embodiment, the proximal portion of the catheter may contain ahemostatic assembly or adapter to prevent back bleeding through thecatheter around the pressure transducer system and to prevent theentrainment of air during transducer insertion and advancement. In oneembodiment, the introducer sheath is made of transparent tubing, such asacrylic, advantageously allowing the operator to verify that all airbubbles have been flushed from the introducer sheath before it isinserted through the hemostatic adapter of the delivery sheath.

In one embodiment, the transducer module and/or its fixation anchors mayhave radiographic markers to enhance visualization during deployment.The legs of the distal anchor may be positioned at the distal end of thedelivery catheter, which can be visually verified under fluoroscopy bynoting the alignment of the distal radiopaque marker on the distal endof the delivery catheter with that on the distal end of the sensorassembly.

In one embodiment, the sensor lead is configured to accept a stylet thatis preferably configured to provide sufficient column strength to allowthe anchor and sensor assembly to be held in place relative to theseptum during deployment, while the catheter is retracted to expose anddeploy the distal anchor legs. Alternatively, the catheter can be heldin place and the stylet and sensor assembly can be advanced to deploythe distal anchor legs.

In one embodiment, a physiological sensing device optimized forplacement in the left atrium of the heart by a percutaneouscatheter-based procedure that traverses the intra-atrial septum isprovided.

In one embodiment, a physiological sensing device optimized forplacement in a pulmonary vein by an open surgical procedure is provided.

In one embodiment, a transducer system optimized for placement throughthe free wall of the left atrium, or through the wall of the left atrialappendage, or across the right atrial free wall or right atrialappendage or transmurally into the main or branch pulmonary arteries bya minimally invasive thorascopic surgical procedure or by a traditionalopen surgical approach is provided.

In one embodiment, intrathoracic pressure may be monitored by placementof the pressure transducer system through the chest wall ordiaphragmatic respiratory muscles by local puncturing techniques, underdirect or fiberoptic endoscopic vision, or by robotic surgicalmanipulation.

In one embodiment, a physiological sensing device is provided, whereininternal transducer components comprising a transducer, power, andcommunications components are enclosed in a hermetic casing or housingcalled a transducer module. The casing comprises metal, ceramic, orglass, alone or in combination, or other constituents known to skilledartisans for constructing hermetic packaging. The distal end of themodule comprises at least one hermetic diaphragm designed to translateor flex in response to pressure changes at the desired location. Thediaphragm or membrane is mechanically coupled to enclosed transducercomponents. The sensor package may be provided in a wide range of sizesand shapes. The sensor package is cylindrical in shape with a distal endand a proximal end. In one embodiment, the module is between about 1 mmand 5 mm long, and 3 mm in diameter. In another embodiment, the moduleis between about 5 mm and about 15 mm long. In another embodiment, thepackage is about 8 mm long, and about 3 mm in diameter. In oneembodiment, the package is less than about 1 mm in diameter. In anotherembodiment, the package is less than about 10 mm long. In oneembodiment, the package may be rectangular, square, spherical, oval,elliptical or any other shape suitable for implantation. In oneembodiment, the sensor package is rigid, and in another embodiment, thesensor package is flexible. In one embodiment, the sensor moduleincludes a cylindrical housing comprising one or more component piecesof titanium CP, titanium 6-4, or other suitable biocompatible metallicalloy or other material suitable for making a hermetic package such asceramic material like alumina or zirconia. One embodiment of theinvention comprises a titanium cylindrical housing, and a diaphragmcomprising a titanium foil that is diffusion bonded or otherwisehermetically affixed to the titanium housing. In another embodiment, thediaphragm and housing may be machined, lapped, or otherwise manufacturedfrom titanium bar or rod stock so that part of the cylindrical housingand the diaphragm are one piece.

In one embodiment, enclosed transducer components are provided,comprising semiconductors that control power, pressure signaltransduction, local signal processing, and data telemetry. Resistivestrain gauges are bonded, or otherwise coupled, to the inside surface ofthe diaphragm.

In one embodiment, a titanium cylindrical housing comprising anapplication-specific integrated circuit (ASIC) or “measurementelectronics” is provided. Measurement electronics are contained withinthe housing and electrically connected to the strain gauges by fine goldwires or other means of electrical connection. In one embodiment, theproximal end of the housing is sealed by a zirconia ceramic feed-throughthat is brazed to a titanium cylinder. In one embodiment, the housingcontains a gaseous atmosphere. In one embodiment, a gaseous atmosphereis provided, which may comprise helium, argon, or any other advantageousgas or combination of gases known to skilled artisans. In oneembodiment, a moisture-absorbant material is included within thehousing. In one embodiment, the housing is evacuated prior to sealing.An electrical insulating liquid such as an oil or other electricallyinsulating liquids known to skilled artisans may be contained within thehousing. In one embodiment, the implanted module contains an internalpower source, such as a battery. In another embodiment, the module ispowered transcutaneously by induction of radio frequency current in animplanted wire coil connected directly to the module or connected by aflexible lead containing electrical conductors, to charge an internalpower storage device such as a capacitor. In one embodiment, thepressure sensor is fabricated by micro electromechanical systems (MEMS)techniques.

In one embodiment, a method for hermetically sealing a silicon device isprovided. The silicon device is coupled to a sensor, such as a pressuretransducer, which benefits from having direct contact with itsenvironment (the body). In one embodiment, a method to hermetically sealthe non-sensing portion of a silicon device while allowing the sensingportion (e.g. the pressure transducer) to have direct contact with thebody is provided. A silicon chip, a gold preform and a metallic housingare each primed for sealing and are assembled. The assembly is thenheated to react the gold preform to the silicon chip and to form amolten gold-silicon alloy in-situ to bind said metallic housing to thenon-sensing portion of the silicon chip. In this way, the non-sensingportion of the silicon chip is hermetically sealed, while stillpermitting exposure of the sensing portion of the silicon chip to theenvironment

In one embodiment, a physiological sensor system is provided with aconfiguration similar to a cardiac pacemaker, with a hermetically sealedhousing implanted under the patient's skin (subcutaneous) and a flexiblelead containing signal conductors with a hermetically sealed pressuretransducer module at its distal end. The signal conductors may beelectrical, fiber optic, or any other means of signal conduction knownto skilled artisans. The lead may have a stylet lumen to aid withtransducer deployment in the body of a medical patient. The lead mayhave a lumen for connection of the sensor module to a referencepressure. In one embodiment, the housing contains a battery,microprocessor and other electronic components, including transcutaneoustelemetry means for transmitting programming information into the deviceand for transmitting physiological data out to an externalprogrammer/interrogator.

In one embodiment, an implanted pressure sensor-lead combination isprovided that is an integral part of a cardiac rhythm management systemsuch as a pacemaker or defibrillator or various other implantablecardiovascular therapeutic systems known to skilled artisans.

In one embodiment, a physiologic sensor system is provided, in which thesignal processing, and patient signaling components are located in adevice external to the patient's body in communication with an implantedsubcutaneous housing via any one or more of the various forms oftelemetry well known in the art, such as two-way radio frequencytelemetry. The subcutaneous housing can comprise only a tuned electricalcoil antenna, or a coil antenna in conjunction with other components.Other designs for antennae are well known to those skilled in the artand are can be used in accordance with several embodiments of thepresent invention. In still another embodiment, the sensor module isdirectly connected to a coil antenna by short lead or lead of zerolength such that the entire system resides in the heart. Such a systemmay have a small internal battery or power could be deliveredtranscutaneously by magnetic inductance or electromagnetic radiation ofa frequency suitable for penetrating the body and inducing a voltage inthe implanted coil antenna. In one embodiment, radiofrequencyelectromagnetic radiation is used with a frequency of about 125 MHz. Inone embodiment, an implantable pressure sensing module that alsocomprises one or more sensors in addition to the pressure transducer isprovided.

In one embodiment, a physiologic sensor system is provided, comprising aplurality of pressure transducers to measure pressures in the transmuralspace or locations proximal to the transmural space, or to measuredifferential pressure between the distal diaphragm and another location.

In one embodiment, a physiologic sensor system is provided, comprising apressure transducer and one or more other types of sensors, said sensorsincluding accelerometers, temperature sensors, electrodes for measuringelectrical activity such as the intracardiac electrogram (IEGM), oxygenpartial pressure or saturation, colorimetric sensors, chemical sensorsfor glucose or for sensing other biochemical species, pH sensors, andother sensor types that may be advantageous for diagnostic purposes, orfor controlling therapy.

In one embodiment, pressure sensors with a frequency response of betweenabout 500 and 2000 Hz are provided.

In one embodiment, pressure sensors with a frequency response of lessthan about 500 Hz and greater than 2000 Hz are provided.

In one embodiment, an implantable pressure sensor module comprising aseparate hydrophone sensor is provided.

In one embodiment, an implantable sensor module that serves dualdiagnostic and therapeutic functions is provided. Said sensor modulecontains at least one electrode for stimulating the organ in which it isplaced. Said electrode or electrodes may be used for electrical pacingthe left atrium

In one embodiment, a method for generating a signal indicative ofpressure in the left atrium is provided, based on components of apressure waveform that are relative to each other and therefore do nothave to be compensated for atmospheric pressure and are not subject tooffset drift. In one embodiment, a method for generating a signal isprovided, wherein the components of a pressure waveform comprise thepressure differential between the mean and respirator minima of the leftatrial pressure waveform. The components of a pressure waveform comprisethe relative heights and/or shapes of the left atrial “a,” “c,” and “v”waves. Decreased left ventricular compliance is the diagnosis when the“a” wave increases without shortening of the atrioventricular (AV) delayor in the presence of mitral stenosis. Increases in the “v” waveamplitude and merging with the “c” wave to produce a “cv” wave isusually indicative of acute mitral valve regurgitation. In anotherembodiment, atrial fibrillation and atrial flutter are detected byanalysis of the LAP waveform. In another embodiment, spectral analysisof the LAP versus time signal is performed.

In one embodiment, a physiologic sensor system comprising components toobtain a signal indicative of pressure relative to atmospheric pressureis provided. An implanted apparatus for measuring absolute pressure at alocation within the body is provided as above, which furthercommunicates this information, as either an analog or digital signal, toan external signal analyzer/communications device. The external signalanalyzer/communications device further contains a second pressuretransducer configured to measure the atmospheric (barometric) pressure.The analyzer/communications device performs a calculation using theabsolute pressure from the implanted module and the atmospheric pressureto obtain the internal pressure relative to atmospheric pressure, thatis, difference between the absolute pressure at the location within thebody and the absolute barometric pressure outside the body. In oneembodiment, gauge pressure measurements are performed only when theimplanted apparatus is queried by the external analyzer/communicationsdevice. In one embodiment, this is accomplished by having the externaldevice supply operating power to the implant module to make themeasurement. In another embodiment, this is accomplished by requiring aproximity RF link to be present between the external and implantablemodules, immediately before, after and/or during the measurement. Inanother embodiment, differential pressure is obtained by the leadcontaining a lumen that communicates a reference pressure to the sensormodule as well known to skilled artisans.

In one embodiment, an implantable pressure sensor module is provided,wherein the module is associated with proximal and distal anchoringsystems that assure localized fixation of the distal end of the moduleand transducer diaphragm essentially coplanar with the plane of theblood contacting surface of the desired chamber or vessel. The anchoringdevice is configured to cross the septum between the right and leftatrium and trap itself between the two chambers such that apressure-sensing member is exposed to the left atrium. In oneembodiment, the distal anchor legs bend outwards until they aresubstantially perpendicular to the longitudinal axis of the cylindricalbase portion of the sensor module. In alternative embodiments, thedistal anchor legs bend proximally until they are oriented at more than90° to the longitudinal axis of the cylindrical base portion of thesensor module. In such embodiments, the angle θ (which represents theamount beyond a perpendicular to the longitudinal axis that the distalanchor legs can bend) can be between about 0° and about 200. In someembodiments, the angle θ can be between about 50 and about 15°. In onespecific embodiment, the angle θ can be about 100. In one embodiment,the angle θ will preferably be reduced to zero degrees when the distalanchor is deployed on a distal side of a septum wall with a proximalanchor on the proximal side of the wall due to the opposing force of theproximal anchor. In one embodiment, the angle θ is selected along with aspring constant of the distal anchor legs such that an opposing forceapplied by the proximal anchor through a septum wall of a particularthickness will cause the angle θ to be substantially reduced to zero orto deflect a small amount in the distal direction so as to conform witha substantially concave left atrial septal surface. In one embodiment,the distal anchor legs are configured such that when both the distal andthe proximal anchors are deployed, contact between the distal anchorsand the septal wall is distributed over the entire proximal side surfacearea of the distal anchor legs to minimize pressure-induced necrosis ofthe septum. The device is configured in a manner that will allow it toposition the pressure-sensing member at a desired location relative tothe septal wall while conforming to anatomical variations. In oneembodiment, the diaphragm is essentially coplanar with the left atrialside of the intra-atrial septum. In one embodiment, the term“essentially coplanar” is defined as the plane defined by the outersurface of the diaphragm is within about ±0.5 mm distance of the planetangential to the left atrial side of the intra-atrial septum at thelocation it is traversed by the pressure-monitoring module. In anotherembodiment, this distance is defined as about ±1 mm. In yet anotherembodiment of the present invention, this distance is defined as about±2 mm. In one embodiment, the device is designed such that the diaphragmwill not be recessed within the septal wall. In one embodiment thedevice is designed so that the surface of the diaphragm is positionedbetween 1 mm and 3 mm distally into the left atrium from the left atrialside of the intra-atrial septum.

According to one embodiment, the sensor system comprises a proximalanchor having one or more helical legs extending between a proximal ringand a distal ring. In one embodiment, the helical path of the proximalanchor legs passes through 360 degrees between the proximal ring and thedistal ring. In alternative embodiments, the proximal anchor can belonger and/or the legs can pass through 720 degrees. In one embodiment,the legs pass through a substantially whole number of complete circlesbetween the proximal and distal rings.

In one embodiment, an implantable sensor module is provided, comprisinga proximal anchor having anchor legs, wherein the at least one of theanchor legs is configured to bend outwards and distally until in theirfully expanded state, each leg forms a loop with a distal most edge thatis positioned substantially distally from the distal edge of the distalring. In one embodiment of the proximal anchor, the anchor assembly isconfigured such that, in a free space (i.e. with no tissue or materialbetween the proximal and distal anchors), the distal edge of theproximal anchor leg loops and the proximal tissue-contacting surface ofthe distal anchor can actually overlap by up to about 0.06″. In someembodiments the overlap can be between about 0.03″ and about 0.05″, andin one embodiment, the distance is about 0.04″. In some non-overlappingembodiments, the distance between the distal edge of the proximal anchorleg loops and the distal edge of the distal ring of the proximal anchorcan be between about 0.040″ and about 0.070″. In some embodiments, thedistance is between about 0.050″ and about 0.060″, and in one particularembodiment, the distance is about 0.054″

In one embodiment, an implantable sensor module is provided, comprisinga proximal anchor having anchor legs with sufficient resilience thatthey relax to positions that overlap the plane of the relaxed distalanchors, assuring that the assembly will be securely anchored to eventhe thinnest of septum walls. In one embodiment, an implantable sensormodule comprises a proximal anchor, wherein the material and dimensionsof the proximal anchor legs are selected such that the elasticity of thelegs is matched to that of the tissue wall with which it is to be incontact, minimizing pressure-induced tissue necrosis and erosion of thedevice through the septum. In one embodiment, the device also comprisesa distal anchor having one or more legs.

In one embodiment, an implantable sensor module is provided, comprisinga proximal anchor with one or more barbs oriented such that the sensormodule can be pulled proximally through an opening in a septal wall, butsuch that the barbs prevent the module from being pushed distallythrough such opening. In one embodiment, the barbs comprise angledmetallic tabs.

In one embodiment, an implantable pressure sensor module is provided,wherein the module comprises a hermetically sealed pressure transducermodule configured to be supported by the proximal and distal anchors.The proximal and distal anchors of this embodiment are configured to bemovable between a collapsed delivery position and an expanded positionin which the proximal and distal anchors secure the module to a wall ofan organ within a patient. Said implantable pressure sensor modulewherein the forward orientation of the distal anchors legs projectdistally beyond the pressure-sensing diaphragm, and protect thediaphragm from being damaged during handling or catheter passage intothe body.

In one embodiment, a system for diagnosing and/or treating a medicalcondition in a patient is provided, using a device to measure pressurecomprising a pressure-sensing module configured to be implanted within apatient, a proximal anchor comprising at least one helical legconfigured to expand from a compressed state to a relaxed state, and adistal anchor comprising at least one leg configured to expand from acompressed state to an expanded state. In one embodiment, said proximalanchor and said distal anchor are configured to sandwich an atrialseptum wall (or the left atrial free wall, the pulmonary vein wall, orany other suitable wall of a heart or a blood vessel) between theproximal anchor leg and the distal anchor leg and to support the modulein the septum wall. In one embodiment, said system further comprises adelivery system, such as a catheter, configured to deploy the sensor,the proximal anchor and the distal anchor in the septum wall.

In one embodiment, a system for monitoring a patient for congestiveheart failure is provided, comprising an implantable pressure transducerand a means for contacting a proximal side or wall and a distal side orwall of an organ to anchor said pressure transducer to the organ wall.Said system for monitoring a patient for congestive heart failure mayfurther comprise a means for delivering said implantable transducer andmeans for contacting to said organ wall.

In one embodiment, a method of monitoring congestive heart failure in apatient is provided, comprising providing a pressure sensor secured to aproximal anchor and a distal anchor, and delivering the pressure sensorthrough a hole in an atrial septum of the patient's heart. The methodfurther comprises deploying the pressure sensor with the proximal anchoron a proximal side of the septum, and the distal anchor on a distal sideof the septum, and monitoring a fluid pressure in the left atrium of thepatient's heart.

In one embodiment, a method of monitoring congestive heart failurewithin a patient is provided, comprising providing an implantablepressure transducer and coupling said implantable pressure transducer toa means for anchoring said pressure transducer in an organ wall. Themethod may further comprise delivering said pressure transducer and saidmeans for anchoring to said organ wall, and causing said means foranchoring said pressure transducer in said organ wall to expand, therebycapturing said organ wall and anchoring said pressure transducerthereto.

In one embodiment, a method of anchoring a device in the heart of apatient is provided, comprising providing an implantable cardiacanchoring device comprising a proximal anchor having at least onehelical leg and a distal anchor having at least one linear leg,attaching an implantable pressure-sensing module to the implantablecardiac anchoring device, positioning a tubular delivery catheter in awall of a patient's heart, and inserting the implantable module and theimplantable cardiac anchoring device into the tubular delivery catheter.The method further includes deploying the sensor and the implantablecardiac anchoring device such that the sensor is retained in atransverse orientation relative to the wall.

In one embodiment, an implantable sensor module is provided, comprisinga substantially cylindrical body connected to the distal end of a lead,and a lead-attachment interface comprises a series of annular notcheswhich can be engaged by a tightly-wound coil. The lead-attachmentmechanism can be welded in place, such as by laser welding, on thesensor. The lead-attachment interface can comprise screw threads.

In one embodiment, an implantable sensor module having a substantiallycylindrical body is provided, to which is attached a distal anchorassembly, wherein the distal anchor assembly is secured to the sensor bystruts or locking tabs on the anchor, which engage an angled annulargroove which circumscribes a distal portion of the sensor, and compriseslocking tabs extending distally from the distal anchor that are bentslightly radially inwards such that they will engage the distal annulargroove in the sensor.

In one embodiment, an implantable sensor module having a substantiallycylindrical body is provided, to which is attached a proximal anchorassembly, wherein the proximal anchor assembly comprises locking tabsconfigured to engage a proximal annular groove in the sensor modulebody.

In one embodiment, an implantable sensor module having a substantiallycylindrical body is provided, to which is attached a proximal and/ordistal anchor assembly, wherein the proximal and/or distal anchorassembly is secured to the sensor by struts or locking tabs on theanchor, which engage an angled annular groove which circumscribes aproximal and/or distal portion of the sensor, and wherein the proximaland/or distal anchor tabs are spot-welded to their respective annularflange to prevent rotation of the anchors relative to the sensor module.

In one embodiment, an implantable sensor module having a substantiallycylindrical body is provided, to which is attached a proximal and/ordistal anchor assembly, wherein the proximal and/or distal anchorassembly is secured to the sensor by struts or locking tabs on theanchor, which engage angled notches that receive the locking tabs in asingle rotational orientation on the sensor, effectively preventingrotation of the anchors with respect to the module.

In one embodiment, an implantable sensor module with a distal sensormembrane and a distal anchor is provided, wherein the distal anchor isconfigured to position the plane of the sensor membrane at apredetermined distance from the plane of the distal anchor. In oneembodiment, the distance is preferably zero, i.e., the pressure-sensingface is preferably substantially co-planar with the distal-most point ofa deployed distal anchor. In alternative embodiments, the sensor ismoved distally such that the pressure-sensing face extends distallyoutwards from the distal anchor. Alternatively still, the sensor issupported within the distal anchor such that the sensor face is recessedwithin the distal anchor. The location of the sensor face relative tothe distal anchor is varied by changing the location of the distalannular groove and/or by varying a size of the locking tabs.

In one embodiment, an implantable sensor module having a substantiallycylindrical body is provided, said module having proximal and distalanchor assemblies, wherein the components are attached to one anotherwith interlocking mechanical fasteners. The proximal anchor, the distalanchor, and the sensor may include interlocking structures configured tomechanically interconnect the assembly components in such a way as tolimit both axial and rotational movement of the components relative toone another. The distal anchor comprises a plurality of fingers thatextend proximally from the cylindrical base portion, each fingercomprising a narrow neck section and a wider proximal tab section. Theproximal anchors may comprise correspondingly shaped slots in the distalring to receive the fingers of the distal anchor. The sensor alsoincludes corresponding interlocking structures configured to engagestructures on the distal and/or proximal anchors.

In one embodiment, an implantable sensor module having a substantiallycylindrical body is provided, said module having proximal and distalanchor assemblies, wherein the sensor includes raised sections aroundthe circumference of the cylindrical body positioned so as to leave gapsfor receiving the neck sections of the fingers, providing a secure andsubstantially immobile connection between the proximal anchor, thesensor, and the distal anchor. The raised sections are machined into thecylindrical body of the sensor. The raised sections comprise independentsegments welded, adhered, or otherwise secured to the cylindrical bodyof the sensor. The interlocking structures may also be welded togetheronce they are assembled, thereby further securing the connection.

In one embodiment, one or more radiopaque markers are used inconjunction with deployment of the physiological sensor. In oneembodiment, radiopaque markers can be applied to the legs of the distalanchor. In one embodiment, radiopaque markers can be applied to theproximal ring of the proximal anchor. In one embodiment, radiopaquemarkers can be applied to other portions of the proximal or distalanchors, or on the sensor. In one embodiment, radiopaque markers arepreferably placed in “low flex zones,” such as the tips of the distalanchor legs and the proximal ring of the proximal anchor. In oneembodiment, radiopaque markers are made of noble metals, such as gold,platinum/iridium, tantalum, etc. In one embodiment, radiopaque markersare attached to the anchor by selective plating or ion beam deposition.In one embodiment, radiopaque markers could be micro rivets and/or ringsthat are mechanically attached to portions of the system components. Inone embodiment, the radiopaque material can be selected to have agalvanic corrosion potential that is substantially similar to a galvaniccorrosion potential of the material from which the anchors and/or sensorare made. If the anchors are to be made of nitinol, the radiopaquemarkers can be made of tantalum. In one embodiment, an electricallyinsulating coating (conformal coatings) such as parylene or otherbiocompatible synthetic material can be used to cover the radiopaquemarkers in order to isolate the marker and anchor section from exposureto the blood or other bodily fluid.

Several embodiments of the present invention provides these advantages,along with others that will be further understood and appreciated byreference to the written disclosure, figures, and claims includedherein.

BRIEF DESCRIPTION OF THE DRAWINGS

The structure and operation of the invention will be better understoodwith the following detailed description of embodiments of the invention,along with the accompanying illustrations, in which:

FIG. 1 is a perspective view of one embodiment of a distal anchor in acompressed state for deployment in a patient.

FIG. 2 is a perspective view of the distal anchor of FIG. 1 in anexpanded state.

FIG. 3 is a perspective view of one embodiment of a proximal anchor in acompressed state.

FIG. 4 is a perspective view of the proximal anchor of FIG. 3 in anexpanded state.

FIG. 5 is a side view of the proximal anchor of FIG. 4.

FIG. 6 is a front view, looking proximally at the proximal anchor ofFIG. 5.

FIG. 7 is a front view, looking proximally at a distal anchor and asensor mounted to the distal anchor.

FIG. 8 is a cross-sectional view of the distal anchor and sensor of FIG.7 taken through line 8-8.

FIG. 9 is a detail view of a portion of the distal anchor and sensor ofFIG. 8, taken at line 9-9.

FIG. 10 is a perspective view of one embodiment of an assembly of aproximal anchor, a distal anchor, and a sensor.

FIG. 11 is a detail view of a portion of the assembly of FIG. 10, takenthrough line 11-11.

FIG. 12 is an exploded view of the proximal anchor, distal anchor andsensor of FIG. 10.

FIG. 13 is a perspective view of an alternative embodiment of a distalanchor in an expanded state.

FIG. 14 is a perspective view of an alternative embodiment of theproximal anchor.

FIG. 15 is a perspective view of a delivery catheter with a portion of adistal anchor visible at the distal end of the delivery catheter.

FIG. 16 is a perspective view of the assembly of FIG. 15 shown with thedelivery catheter removed to show detail.

FIG. 17 is a perspective view of a distal anchor and a sensor deployedon a distal side of an atrial septum wall.

FIG. 18 is a perspective view of the distal anchor and sensor of FIG. 17with the delivery catheter further retracted.

FIG. 19 is a perspective view illustrating a delivery catheter deployingan anchor and sensor assembly as viewed from a proximal side of anatrial septum wall.

FIG. 20 is a side view of an anchor and sensor assembly deployed andanchored to a thin atrial septum wall (shown in cross-section).

FIG. 21 is a side view of an anchor and sensor assembly deployed andanchored to a thicker atrial septum wall (shown in cross-section).

FIG. 22 is a schematic view of an implantable transmural pressuresensor.

FIGS. 23A and 23B are elevational and cross sectional views of oneembodiment of the implantable pressure sensor.

FIG. 24 shows the results of an experiment evaluating the effect ofdiaphragmatic concavity (depth of a central concavity) in a 25 micronthick, 2.5 mm diameter titanium foil membrane on transducer sensitivity(gain).

FIG. 25 is a graph comparing transducer calibration functions 1 monthbefore deployment and 18 weeks following deployment in a pig.

FIG. 26 illustrates various embodiments of the distal anchor legs.

FIGS. 27A to 27C depict deployment of one embodiment of the distalanchor legs.

FIG. 28 is a perspective view of the distal anchor legs from FIG. 27C.

FIGS. 29A and 29B are perspective views of the distal anchor legs fromFIG. 27C.

FIG. 30 is a side view of an anchor and sensor assembly where the sensordiaphragm is generally coplanar with the distal anchor and the leftatrial surface of the septal wall, showing thick tissue overgrowth ofthe diaphragm and distal anchors.

FIG. 31 is a side view of an anchor and sensor assembly where the sensordiaphragm is extended distally from the plane of the distal anchors andthe left atrial surface of the septal wall, showing reduced thickness oftissue overgrowth of the sensor diaphragm.

FIG. 32 is a side view of an anchor and sensor assembly where the sensordiaphragm is surrounded by a cupped distal rim on the sensor housing tominimize coupling between stresses in the septal wall and the diaphragm.

FIG. 33 is a side view of an anchor and sensor assembly where adrug-eluting band surrounding the distal circumference of the sensorhousing is provided. Crossing channels are provided parallel to the longaxis of the housing perpendicular to the drug-eluting band to allow forlimited ingrowth of endothelial cells to cover the sensor diaphragm.

FIG. 34 is a side view of an anchor and sensor assembly in which groovesare provided around the sensor housing distal circumference to anchortissue overgrowth to reduce the coupling of stress between the tissueand the sensor diaphragm.

FIG. 35 is a side view of an anchor and sensor assembly in which tabsare provided around the sensor housing distal circumference to anchortissue overgrowth to reduce the coupling of stress between the tissueand the sensor diaphragm.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Several embodiments of the present invention relate generally toimplantable physiological sensors. Physiological sensors include, butare not limited, to pressure sensors. In one embodiment, a pressuretransducer system that is stable following implantation in the medicalpatient is provided. The sensors and methods described in some of theembodiments are designed for optimal healing and stability of implantedsensors. Several embodiments of the current invention are advantageousbecause they reduce the risk of thrombus formation. Other embodimentsminimize tissue overgrowth that causes pressure sensor drift. Otherembodiments of the invention are designed to isolate the sensordiaphragm from stresses in the tissue surrounding the sensor assembly.Other embodiments of the invention are designed to optimize performance.In one embodiment, deployment devices and/or anchoring means areprovided integral to or accompanying the sensor. In a furtherembodiment, the sensor is enclosed in protective packaging. In anotherembodiment, the sensor is designed to minimize viscoelastic drift. Inyet another embodiment, temperature compensation is provided. In afurther embodiment, the effects of pressure waveform artifacts due tonon-pressure mechanical forces (e.g. “side loading”), are minimized.

Implantable Device Thrombosis and Tissue Overgrowth

Transmural placement of traditional physiologic sensing apparatuses,particularly for the measurement of cardiac chamber or vascularpressures, have a number of limitations that affect long term reliablesensing and may promote serious complications. One area of particularconcern is the placement of these devices through the walls of the heartto contact the blood contained in the left atrium or adjacent regions ofthe left-side of the heart. These devices can activate thrombusformation (blood clots, mural thrombi) on their exposed surfaces or overadjacent injured tissue. Left-sided thrombi have the potential toembolize to arteries of the systemic circulation causing catastrophiccomplications such as cerebral vascular accidents (stroke) and embolicinfarctions of other vital organs.

Several embodiments of the present invention are designed to accommodatefor the long-term presence of a device in the left atrium and itsattendant risk of thromboembolic events, including stroke. In someembodiments, the surface properties of the device, such as its materialconstituents and its roughness, the size of the device, and/or the shapeof the device are designed to minimize the risk of thromboembolicevents. In one embodiment, a pressure transducer system having arelatively small surface area is provided. This embodiment isparticularly advantageous because a smaller surface area accelerateshealing and decreases the chance of clot formation on the device oradjacent injured wall.

Severe local tissue injury and inflammation promotes thrombus formation.Clots can form as platelets are activated in regions of high blood shearrate or where fibrin is deposited in regions of stasis, classically inthe presence of atrial fibrillation. Also, the overall prothromboticstate of the patient is important. Accordingly, in several embodiments,appropriate pharmacologic prophylaxis, including, but not limiting toantiplatelet, antithrombin, and/or antiproliferative drugs, areadministered before, during, and/or after implantation of the sensor. Inone embodiment, pharmacologic treatments are used to accelerate orfacilitate coverage of the device with new tissue growth (overgrowth),which is referred to as a neoendocardium in the case of the heart or aneointima in the case of a blood vessel. As used herein, the termsneoendocardium, neointima, tissue overgrowth, tissue in-growth are usedinterchangeably. Once tissue overgrowth occurs there often develops anew lining of cells that normally form the blood tissue interface call aneoendothelium. Generally, a functional neoendothelium reduces the riskof an underlying implanted device generating mural thrombus.

In several embodiments of the current invention, one or more of thefollowing factors is addressed in order to decrease the risk of thrombusformation: a rough implant surface, the extent of adjacent tissueinjury, interruption of laminar blood flow during deployment, high shearrate of the blood contacting the implant, local blood stasis, anddelayed coverage of the device by body tissues.

According to our own studies with stents, we have observed that when arelatively a rough metallic surface (bead blasted nitinol or 316 Lstainless) is exposed to rapid blood flow with a high shear rate,exaggerated platelet activation and aggregation are triggered resultingin the formation of platelet-rich thrombi. Accordingly, in severalembodiments, at least a portion of the metallic surface of the device iselectropolished to reduce the risk of acute thrombosis. In oneembodiment, the entire metallic surface is electropolished. In anotherembodiment, chemical, mechanical, and/or sonic treatments, including,but not limited to passivation and oxygen cleaning, are used to achievesimilar effects to electropolishing.

Stent studies have also shown that thrombosis is most likely during thefirst two to three weeks after implantation until a neoendothelium ispresent. Further, when tissue overgrowth is delayed or prevented, suchas by treatment with intravascular radiation therapy (brachytherapy) atthe time of implantation, there is at increased risk for delayedthrombosis (months later). Accordingly, in several embodiments of thepresent invention, antiplatelet agents are administered to the patientto reduce the risk of thrombosis. In one embodiment, aspirin and/orclopidogrel, are administered to reduce the incidence of thrombosis.

Although not wishing to be bound by the following theory, it is believedthat as soon as the device's appropriate surface is covered by anovergrowth of proliferating tissue (neointima), especially when theneointima contains a blood lining barrier of cells call aneoendothelium, the risk of thrombosis is substantially reduced oressentially eliminated. Tissue overgrowth is the natural healingresponse to local vascular mechanical injury. The sequence of healingevents include coverage of the device with plasma proteins such asalbumen and fibrin during the initial hours to days, recruitment ofblood mononuclear cells over the first week that signal vascular smoothmuscle cells in the vessel wall to migrate to the lumen surface,proliferate, and secrete a proteoglycan extracellular matrix. One of theimportant signals for turning off smooth muscle cell proliferation isin-growth of vascular endothelial cells from adjacent, uninjured tissue.In several embodiments of the current invention, the device is designedto facilitate or accelerate tissue in-growth. In one embodiment,in-growth is enhanced by providing shallow channels on the surface ofthe device oriented in the direction of blood flow to aid thismigration. In some embodiments, complete coverage should take about 2 to3 weeks, and the rapidity of this overgrowth is desirable because itlowers the risk of thromboembolism and shortens the need for adjunctiveantiplatelet medication.

Tissue thickness tends to reach a maximum after about 4 to 6 months,averaging about 300 to 400 microns thick depending on the stent andstudy. When this thickening encroaches on the vessel lumen causingluminal narrowing of more than 50% of the vessels reference diameter itis called restenosis. After the first 6 months, the extracellular matrixis gradually replaced by collagen and the tissue distribution may change(remodeling) but generally the tissue remains intact and stable for manyyears thereafter. The tissue remains pliable and only rarely, if ever,becomes atherosclerotic or calcified. The maximal thickness of tissueovergrowth is highly variable but is well known to depend on and avariety of host risk factors, such as diabetes and smaller vessel size.Tissue thickness also depends on mechanical factors including the extentof tissue injury and device design characteristics. In one embodiment ofthe present invention, the pressure transducer system is designed tohave a lower profile or less strut protrusion into the blood stream,thereby promoting a thinner covering of neointima. In other embodiments,the sensor system is designed to develop a thin layer of neointima thatprovide remodeling benefits to reduce turbulent bloodflow about thesensor system.

Several embodiments of the present invention provide a physiologicalsensor system that is constructed from a material that is minimallyreactive, stable, and that promotes a favorable healing response.Several embodiments of the present invention are particularlyadvantageous because they minimize thrombotic potential, promote rapidtissue coverage, heal without chronic inflammation, and/or develop athin neointima with beneficial remodeling features. Other advantages ofsome embodiments include sensor reliability and accuracy, positioningstability and clinical efficacy for diagnosing and directing therapy inchronic CHF. In one embodiment, the sensor system comprises one or moreof the following materials: alloys of stainless steel, nitinol,titanium, cobalt chromium, and tantalum. One skilled in the art willunderstand that several other biocompatible materials may be used. Thesematerials are typically minimally reactive or non-reactive. Usingminimally reactive or non-reactive materials is particularlyadvantageous because they are hemocompatable and do not promote aninflammatory tissue reaction known to pathologists as a foreign bodyreaction consisting of granulomas containing macrophages and giantcells. This type of tissue reaction may be associated with higherthrombotic complication rates, more exuberant tissue proliferation andthickening, calcification and possibly even late tissue breakdown anddelayed exposure of bare reactive surfaces to blood once again promotingthrombus formation.

In some embodiments, the implantable sensor system will be operable toelute one or more drugs that affect neointimal tissue thickness orthrombosis risk. In some embodiments, a component of the sensor willelute the drug. In an alternative embodiment, a separate device,administered in conjunction with the sensor, will elute the drug. In oneembodiment, antiproliferative drugs, such as from biostable orbioerrodable polymeric coatings (including, but not limited to,sirolimus and paclitaxel) are used to control neointimal tissuethickness and virtually eliminate restenosis. In some embodiments,pharmacologic treatment will reduce tissue thickness by more than 50%,to an average of about 120 microns. In certain embodiments of theinvention, more precise control of drug delivery is desired because highdrug doses may in some cases create toxic reactions or prevent anyeffective tissue coating and increase the likelihood of late (afterthree weeks) stent thrombosis. Accordingly, in several embodiments ofthe present invention, low doses of one or more of these drugs elutedover longer periods are provided. The skilled artisan will understandthat while reduced neointimal thickness may be desirable, it isdesirable for implant surfaces in contact with blood be covered with atleast a thin layer of endothelial cells. One skilled in the art willunderstand that endothelial cells grow over the surface of an implantedsurface from its contact with existing tissue. In one embodiment, one ormore pathways or channels are provided to encourage the ingrowth ofendothelial cells while reducing neointimal thickness. In oneembodiment, anti-thrombotic compounds are eluted from the implanteddevice. Elution of anti-thrombotic compounds may be used as a bridge toreduce the thrombosis risk until such time the device can develop aneoendocardium covering.

One skilled in the art will understand that an antiproliferative and/orantiplatelet drug regimen can be adjusted to the type of sensorimplanted, the location of the implant, and the condition of thepatient, and other factors. For example, pharmacologic treatment can beadministered in accordance with U.S. Pat. No. 6,152,144 (Lesh) and U.S.Pat. No. 6,485,100 (Roue et al), herein incorporated by reference, whichdescribe permanently implanted devices placed in the left atrium torepair transmural congenital defects of the intra-atrial septum. In oneembodiment of the present invention, thromboemboli are prevented withantiplatelet therapy consisting of about six months of aspirin therapy.In one embodiment, aspirin therapy is augmented with a secondantiplatelet agent, such as clopidogrel, for approximately the firstthree months.

In one embodiment of the invention, the sensor system is designed tominimize tissue erosion that may be related to mismatching of theelasticity of the anchoring portions versus the surrounding tissue. Itis well known to those skilled in the art that orthopedic prosthesesthat differ significantly in elasticity from bone produce stressshielding of the bone, resulting in its weakening and producing problemswith the prostheses. It is also well known to skilled artisans that softtissue prostheses such as fabric patches and tubes used in vesselreplacement and repair are best tolerated when their elasticity issimilar to that of the surrounding tissues to which they are attached.In one embodiment, the elasticity mismatch of the sensor system and thesurrounding tissue can be assessed by calculating the difference in theelastic modulus (dyn/cm²) between the sensor system material and thesurrounding body tissue at a given pressure. The elastic modulus can bemeasured by calculating the change in stress over the change in strainof a given material or tissue.

Several embodiments of the current invention are designed to treat CHF.CHF patients have a high incidence of thromboembolic stroke in partbecause they have a high frequency of known risk factors for left atrialthrombi including: generally enlarged and diseased left atria; mitralvalve disease with mitral regurgitation is present in 50%; about 80% ofpatients are age 65 or older; about one third have atrial fibrillation;atherosclerosis, diabetes and hypertension are also very common.Thromboembolic events typically, but not always, result from theinteraction of multiple risk factors. Accordingly, several embodimentsof the invention are particularly advantageous for CHF patients becausethey minimize the incidence of a thromboembolic event by providing animplantable device with reduced thrombogenic effect. Moreover, inaccordance with some embodiments of the present invention, atransmurally implanted left atrial pressure transducer device thatpromotes rapid healing with non-thrombogenic tissue overgrowth is highlydesirable for preventing additional thromboembolic complicationsassociated with the implanted devices in patients with CHF.

Several embodiments of the present invention comprise one or moreanchors, described below, to affix the sensing device to tissue. Tohasten and optimize tissue overgrowth, one embodiment minimizes the pathlengths for tissue to in-grow over the distal anchor fixated to the leftatrial side of the septum by creating slots or holes in the distalanchor legs. In one embodiment, within several weeks after implantation,the entire device is covered with new tissue, including precursorfibrous tissue and endothelium. A covering of endothelium is desirablebecause it prevents the formation of blood clots that, if formed, couldbreak loose and cause a blocked artery elsewhere in the body, mostdangerously in the brain. A covering of fibrous tissue is also a commoncomponent of the body's healing response to injury and/or foreignbodies. In another embodiment, a biocompatible polymeric coating such asparylene is placed on the fixation anchors and diaphragm to minimizeplatelet adhesions and aggregation, to provide electrical insulation,and to prevent corrosion of underlying metallic constituents. In yetanother embodiment, surface grooves or channels are used in at least aportion of the implant to facilitate tissue growth. In one embodiment,at least one groove can be formed on the diaphragm surface or on theanchor legs to serve a similar purpose. The groove's long axes can belinear, circumferential, and serpentine or any other beneficial shapeand the groove's cross section can be rectangular, semi-round, or anyother beneficial shape. In one embodiment, the grooves, wells, orportions or all of the exposed surfaces are filled with or coated bybiostable or bioerrodable polymer or polymers containing agents,including one or more drugs that control the thickness of neointimaltissue overgrowth, or prevent local thrombus formation.

Although tissue overgrowth of the implanted pressure sensor can reducethe thrombosis risk posed by the device, an excessive growth of fibroustissue on the left atrial surface of the pressure sensor may beundesirable because it may interfere with accurate transmission of fluidpressure in the left atrium to a relatively compliant diaphragm. Inaddition, uneven contraction of fibrous tissue over time may causeartifactual changes in the pressure waveform, which could confoundinterpretation of the data. In one embodiment, a coating on thediaphragm surface and or the anchor surfaces inhibits or reduces theformation of undesirable fibrous tissue, while not preventing thebeneficial growth of an endothelial covering. Coatings with theseproperties are well known in the art of implanting medical devices,particularly intravascular stents, into the blood stream. Surfacecoating materials include, but are not limited to, parylene,polyvinylpyrrolidone (PVP), phosphoryl choline, hydrogels, albumen,polyethylene oxide and pyrolyzed carbon. In another embodiment, paryleneis placed on the fixation anchors and diaphragm to minimize plateletadhesion and aggregation, to provide electrical insulation, and toprevent corrosion of underlying metallic constituents.

In one embodiment, at least some areas of the sensor package anddiaphragm are electropolished. Electropolished surfaces are known bythose skilled in the art to reduce the formation of thrombosis prior toendothelialization, which helps prevent device thrombosis and leads to areduced burden of fibrotic tissue upon healing. Metallic intracoronarystents currently approved for clinical use are electropolished for thispurpose.

Release of antiproliferative substances, including radiation and certaindrugs, are also known to be effective in limiting tissue overgrowthafter vascular stenting. Such drugs include, but are not limited to,Sirolimus, Everolimus, Tacrolimus and related antirejection compounds,Taxol and other Paclitaxel derivatives, corticosteroids,anti-inflammatory anti-macrophage agents such as 2-chlorodeoxyadenosine(2-CDA), antisense RNA and ribozymes targeted to cell cycle regulatingproteins and other targets, and other cell cycle inhibitors, endothelialpromoting agents including estradiol, antiplatelet agents such asplatelet glycoprotein IIb/IIIa inhibitors (ReoPro), anti-thrombincompounds such as unfractionated heparin, low-molecular weight heparin,hirudin, hirulog etc, thrombolytics such as tissue plasminogen activator(tPA). These drugs may be released from biodegradable or biostablepolymeric surface coatings or from chemical linkages to the externalmetal surface of the device. Alternatively, a plurality of smallindentations or holes can be made in the surfaces of the device or itsretention anchors that serve as depots for controlled release of theabove mentioned antiproliferative substances, as described by Shanley etal. in U.S. Publication No. 2003/0068355, published Apr. 10, 2003,incorporated by reference herein.

Affects of Tissue Growth on Pressure Sensor Calibration

As described above, tissue overgrowth is desirable to reduce theincidence of thrombosis. Although tissue overgrowth has clear benefits,it may also pose some challenges for implanted pressure sensors becausethe overlying tissue can be a major source of drift, thereby causing thetransducer to lose calibration. For example, calibration issues canoccur with an implanted pressure transducer that relies on thedisplacement of an exteriorly exposed mechanical member, such as amembrane or diaphragm, that actuates protected internal components suchas piezoresistive strain gauges or other types of transducers thatgenerate a signal related to the pressure change. For transducers thathave a linear relationship between the pressure change and thetransducer output and to the extent that tissue overgrowth interfereswith the displacement of the mechanical member in response to a givenpressure change, the sensitivity or “gain” (slope) of the transduceroutput/input relationship will be reduced or drift. Likewise, if tissuecoverage causes displacement of the mechanical member, errors or driftin offset or “zero” (y-intercept) will occur. When these tissue effectscause errors in physiologic pressure measurement that affect diagnosisand treatment decisions, the transducer requires recalibration.Transducers that have non-linear calibration relationships will also beaffected by tissue overgrowth and experience drift.

The process of tissue coverage is generally dynamic. As healing takesplace the thickness of tissue increases over about 4 to 6 months;thereafter, the thickness may gradually decline or increase (remodel)over the next several years. In addition to tissue thickness effects ondrift, the biochemical constituents of the tissue change as the matrixmaterial is replaced with collagen and may have different materialproperties such as elasticity, that may further contribute to transducerdrift.

Recalibration of implanted pressure transducers is typically performedby comparison with a calibrated standard. This most often has meant thatthe patient is required to undergo periodic invasive catheterizationprocedures. Thus, in several embodiments of the present invention, apressure transducer with calibration parameters that are minimallyaffected by tissue overgrowth, thereby reducing the need for invasiverecalibration, is provided. These embodiments are advantageous becausethey do not subject the patient to the risk, discomfort, and expense ofsuch procedures. In some embodiments, a pressure transducer thatpromotes reduced but effective tissue overgrowth is provided. This isdesirable because it reduces the risk of thromboembolic complications.Typically, if tissue overgrowth causes an essentially linear sensor todrift with respect to both gain and offset, recalibration against astandard at a minimum of two different pressures is required. A pressuresensor that drifts with respect to offset only may be more simplyrecalibrated against a standard at a single pressure only. Accordingly,several embodiments of the present invention provide pressuretransducers that either do not require calibration or can be easilyrecalibrated using non-invasive methods. Methodology and apparatus tonon-invasively assess implanted transducer calibration and automaticallyrecalibrate has been described in U.S. Patent Application PublicationNo. U.S. 2004/0019285 A1, herein incorporated by reference.

Protective Packaging

Electronic and mechanical devices are frequently placed in environmentsthat may damage the components unless some form of protection isprovided. For example, some electronic medical devices implanted into abody may be exposed to body fluids that may cause unprotectedsemiconductor circuits and non-electronic components to fail.Accordingly, in several embodiments of the current invention, at least aportion of the sensor system is protected against the damaging effectsof bodily fluids. In one embodiment, the device is contained in hermeticpackaging to limit exposure to these harmful elements.

In some embodiments, a traditional approach to creating protectivepackaging for implantable medical devices is used. This generallyinvolves the complete encasement of the silicon or semiconductorcomponents of the device in a hermetic package. Such packages typicallyutilize a metal such as titanium, or a ceramic material like alumina orzirconia. Various glass materials can also be employed. In otherembodiments, the sensor is enclosed in a metal packaging and theenvironmental pressure is coupled to the sensor through a diaphragmbonded to the packaging. Such approaches place an interface between theenvironment and the sensor for the electronic components to interactwith the environment and to protect the integrity of the device. Such adiaphragm can be made from the same or similar materials as the housingto facilitate bonding and hermetic sealing of the diaphragm with thehousing or protective barrier of the device. Further methods of hermeticsealing are described below.

Delivery and Deployment of the Pressure Transducer

Additional embodiments that enhance or optimize the transmurallyimplanted transducer's capabilities are provided. With respect todeployment apparatus and methodology, in one embodiment, the transducermodule is delivered to its desired location by a catheter or sheath thattransverses the wall of the desired chamber or vessel and can be loadedwith the transducer module system with its fixation anchors in aconstrained or folded configuration. In another embodiment, the deliverycatheter permits simultaneous measurement of fluid pressure from thecatheter tip during transducer package transit and deployment. In afurther embodiment, the delivery catheter permits injection ofradiographic contrast material with the transducer system in its lumento localize positioning during transducer system deployment. In anotherembodiment, the transducer module and/or its fixation anchors haveradiographic markers to enhance visualization during deployment.

Viscoelastic Drift

In several embodiments of the instant invention, the pressure transduceris optimized for assuring performance and minimizing complications. Inone embodiment, the transducer is designed such that viscoelastic driftis minimized. After prolonged exposure to a large change in averageambient pressure, such as the change to lower pressures during travel tohigh altitude, some pressure transducers undergo viscoelastic driftwhereby their components undergo elastic deformation with prolonged timeconstants lasting hours to days or more before returning to thepre-stressed state. This phenomenon may result in a baseline shift thatpersists until another large change in average ambient pressure setsinto motion another viscoelastic drift to another new baseline. In oneembodiment of the present invention, the viscoelastic properties of thepressure transducer are characterized during pre-implant calibration. Inone embodiment, the known viscoelastic properties are used incombination with the recorded pressure variations over time to obtainpressure measurements that are corrected for viscoelastic drift.

In one embodiment, the diaphragm has a plurality of resistive straingauges coupled to the diaphragm's internal surface. In one embodiment,shown in FIG. 22, the diaphragm 302 has two or four resistive straingauges 303, 304 adhered to the diaphragm's internal surface by anadhesive. The adhesive normally serves two purposes: i) fixation of thestrain gauges to the diaphragm and ii) electrical insulation of thestrain gauges to prevent a short circuit to the case. In one embodiment,to accomplish the latter, the adhesive is of a thickness that issubstantial enough to exhibit some viscoelastic displacement in responseto a change in the shape of the diaphragm, resulting in transducer driftin response to large prolonged change in average pressure, such asoccurs when the patient travels to a much higher or lower altitude. Inone embodiment, a silicon dioxide insulation layer is grown on thebottom of the silicon strain gauges providing additional electricalisolation and consequently minimizing the thickness of adhesive andresulting viscoelastic drift.

In another embodiment, a software algorithm is used to automaticallycorrect for viscoelastic drift. In another embodiment, a secondarydiaphragm may be located on other portions of the module. In oneembodiment, a secondary diaphragm is used to measure pressure at asecond site or to measure a differential pressure between the distallylocated diaphragm and the secondary diaphragm. In one embodiment, thesecond diaphragm may be used to provide additional calibrationinformation for the first diaphragm, and/or vice versa.

FIG. 24 shows the results of an experiment evaluating the effect ofdiaphragmatic concavity (depth of a central concavity) in a 25 micronthick, 2.5 mm diameter titanium foil membrane on transducer sensitivity(gain). These data suggest that the lesser the concavity (or convexityfor that matter), that is, the flatter the diaphragm, the higher thegain. Accordingly, in one embodiment, a diaphragm that is bothessentially non-compliant and essentially flat is used to minimize theeffects of tissue overgrowth on reducing transducer gain(non-compliance), while optimizing intrinsic gain (flatness). In anotherembodiment, the diaphragm thickness is maximized to maximize flatnessand minimize compliance, consistent with the sufficient compliance toderive a useable transducer signal.

Temperature Compensation

In one embodiment, the pressure sensor includes temperature compensationso that pressure measurements will be minimally affected or unaffectedby temperature change. In one embodiment, apparatus to measure thetemperature at the site of the sensor is provided. In one embodiment,temperature compensation or modulation is achieved by using multipleresistive strain gauges arranged in a Wheatstone bridge, such that theelectrical voltage output of the bridge is proportional to the ratio oftwo or more resistances, as is well known in the art of electricalmeasurements. By selecting resistive strain gauges with substantiallyidentical temperature coefficients, the intrinsic output of the bridgeis made to be temperature independent. However, in one embodiment, theoverall response of the pressure transducer may still be temperaturedependent due to other factors, such as the different thermal expansionsof the various components and contents of the device. Another embodimentof temperature compensation utilizes an internal thermometer comprising,for example, a resistor whose resistance depends upon temperature in areproducible way, and which is placed in a location isolated from thetransducer diaphragm so that its resistance does not depend on pressurevariations. Prior to implanting the device, calibration data iscollected consisting of the output of the transducer versus pressure asa function of the reading of the internal thermometer. Afterimplantation, the signal from the internal thermometer is used togetherwith the transducer output and the calibration data to determine thetemperature compensated pressure reading. In one embodiment, a band gapvoltage reference is used to create a current proportional to absolutetemperature that is then compared to the temperature-independent voltagereference. Such methods are well known in the art of CMOS integratedcircuit design.

Output Artifacts-Minimizing Effects of Side Loading

Another characteristic of some pressure transducers is that outputartifacts can occur when structures adjacent to the mechanical membersare stressed. Forces placed on the module casing that distort themechanical diaphragm are known as side-loads, Side-loads exerted bytissue contact with the transducer module housing and/or its anchors,and/or forces exerted on the module by its lead, may producenon-pressure-signal artifacts in the output signal. Side-loads maydevelop during the healing process as tissues encroach on the side areasadjacent to the mechanical member supporting the pressure-sensingdiaphragm, causing differential loading of said member. Accordingly, inone embodiment of the invention, the pressure transducer is designed tominimize output artifacts.

In one embodiment, the casing adjacent to the diaphragm is madesubstantially inflexible and non-distortable such that the diaphragm isnot distorted by side-loads under physiologic conditions.

Another embodiment, shown in FIGS. 23A and 23B, comprises two sets ofadherent strain gauges, an inner set 304 near the center of thediaphragm where tangential strain is relatively high and an outer set303 near the periphery of the diaphragm where radial strain is also highbut of opposite polarity. Electrically, this arrangement is connected toform a Wheatstone bridge circuit. In order to make the overalltransducer relatively small, compromises are made on the supportingstructure of the diaphragm. Because the supporting structure is notabsolutely rigid, forces applied to the side of the structure willresult in a small deformation of the diaphragm. The radial strain gaugesare the most affected by this “side load.” Prior art approaches tostrain gauge mounting provide for the two radial strain gauges to beplaced 180° apart. Side forces in line with these gauges would result inmaximum signal change on the bridge since the effects are additive. Alsoside forces 90° from the radial strain gauge axis would produce anothermaximum but opposite polarity signal change on the bridge. In oneembodiment of this invention, the radial strain gauges are oriented 90°from each other rather than the standard 180° orientation. This resultsin a partial canceling of the side load force effects, as the signaleffects are substantially subtractive rather than additive. In thisembodiment, the orthogonal arrangement of the radial strain gauges hasbeen experimentally measured to reduce side loading effects on pressurereadings by about two-thirds compared to when the radial gauges areaffixed about 180 degrees apart.

In a further embodiment, the regions of the transducer module casingwhere the proximal and distal anchors are affixed are located as farproximal from the distal diaphragm as possible so that differentialtension on the anchor legs causes less loading on the module casing nearthe diaphragm and thereby less distortion of the diaphragm than if thefixation regions were more distal and closer to diaphragm.

The skilled artisan will realize that various combinations of theembodiments described above may be beneficial. Therefore, a furtherembodiment represents any combination of the above embodiments,including increased casing wall thickness or rigidity, orthogonalplacement of outer strain gauges, and/or proximal fixation of anchorsutilized to increase pressure transducer insensitivity to side-loads.

Locations and Insertion Routes

In several embodiments, a physiological sensing device comprisingimplantable, transmurally-placed pressure transducer systems formeasuring fluid pressure within a cardiac chamber or a blood vessel isprovided. In one embodiment, the transducer system is implantable withinany hollow viscous within the body of a medical patient. In oneembodiment, the transducer system is optimized for placement in the leftatrium of the heart by a percutaneous catheter-based procedure thattraverses the intra-atrial septum. In another embodiment, the transducersystem is optimized for placement in a pulmonary vein by an opensurgical procedure.

As used herein, the terms “proximal” and “distal” are used to describerelative positions, locations and/or orientations of various components.As used herein, the term “distal” is used in its ordinary sense, andgenerally refers to objects and locations that are further along atrans-vascular path from an operator of a trans-vascular device.Similarly, the term “proximal” is used in its ordinary sense, and referswithout limitation, to objects and locations that are closer along atrans-vascular path to an operator of a trans-vascular device. Forexample, in some embodiments the most proximal end of a catheter is theend that is operated by a clinician performing a procedure within apatient with the catheter. Similarly, in such embodiments thedistal-most end of a catheter is the end placed furthest into the bodyof the patient and furthest from the clinician performing the procedure.The terms “proximal” and “distal” are used herein with reference tocertain embodiments of the orientation of certain components during aprocedure. The skilled artisan will recognize however, that inalternative embodiments the directions of “proximal’ and “distal” asused herein may be reversed with respect to a single component used in asimilar procedure.

Several embodiments of the current invention comprise permanentlyimplantable transmurally-placed pressure transducer systems formeasuring fluid pressure within a cardiac chamber or a blood vessel, orany other hollow viscous or fluid filled space within the body of amedical patient. The term “permanently implantable” as used herein shallbe given its ordinary meaning and shall refers to any and all suchdevices that are intended for implanted for more than about one week andare therefore potentially or substantially permanent. In one embodiment,the transducer system is optimized for placement in the left atrium ofthe heart by a percutaneous catheter procedure traversing theintra-atrial septum. In another embodiment, the transducer system isoptimized for placement in a pulmonary vein by an open surgicalprocedure. In yet another embodiment, the transducer system is optimizedfor placement through the free wall of the left atrium, or through thewall of the left atrial appendage, or across the right atrial free wallor right atrial appendage or transmurally into the main or branchpulmonary arteries by a minimally invasive thorascopic surgicalprocedure or by a traditional open surgical approach. Intrathoracicpressure may be monitored by placement of the pressure transducer systemthrough the chest wall or diaphragmatic respiratory muscles by localpuncturing techniques, under direct or fiberoptic endoscopic vision, orby robotic surgical manipulation. In one embodiment, output from anintrathoracic pressure transducer may be used to compensate for arterialpressure fluctuations caused by a patient's breathing rate and effort.In one embodiment, the intrathoracic pressure transducer can be used tovalidate and/or error check the operating status of other pressuretransducers located in the thoracic cavity by comparing pressuretracings and checking for analogous respiratory fluctuations. In oneembodiment, the intrathoracic pressure transducer is used to measure therespiratory efforts to assess respiratory status.

It will be apparent to those skilled in the art that transmural pressuremonitoring refers in general to monitoring pressure anywhere in the bodywith a pressure transducer system that is placed through the wall of ortraversing a septum, membrane or any other dividing structure thatphysically separates or represents a barrier or boundary of the locationwith the desired pressure to be monitored and other body structures. Itwill also be apparent that several methods of reaching the desiredlocation can be used in accordance with several embodiments of thisinvention depending on the suitability of the specific anatomy to aparticular method. These methods include, but are not limited to,catheter delivery, endoscopic delivery, minimally invasive surgery, andopen surgery. One of skill in the art will understand that any locationand transmural routes and methods of positioning implanted pressuretransducer systems can be used in accordance with several embodiments ofthe present invention.

Pressure Sensor Designs

In one embodiment, the internal transducer components including thetransducer, power, and communications components are enclosed in ahermetic casing or housing called a transducer module. In oneembodiment, the casing comprises metal, ceramic, or glass, alone or incombination, or other constituents known to skilled artisans forconstructing hermetic packaging. The transducer module has proximal anddistal ends. Referring to FIG. 23B, in one embodiment, the distal end ofthe module comprises at least one hermetic diaphragm 302 designed totranslate or flex in response to pressure changes at the desiredlocation. In one embodiment, the diaphragm or membrane is mechanicallycoupled to enclosed transducer components.

In one embodiment, the enclosed transducer components comprisesemiconductors that control power, pressure signal transduction, localsignal processing, and data telemetry. In one embodiment, resistivestrain gauges 303, 304 are bonded, or otherwise coupled, to the insidesurface of the diaphragm 302. In one embodiment, a titanium cylindricalhousing 306 comprises an application-specific integrated circuit (ASIC)307 or “measurement electronics.” Measurement electronics 307 arecontained within the housing and electrically connected to the straingauges by fine gold wires 308 or other means of electrical connection.In one embodiment, the proximal end of the housing is sealed by azirconia ceramic feed-through 310 that is brazed to a titanium cylinder.In one embodiment, the housing contains a gaseous atmosphere. Thegaseous atmosphere may comprise helium, argon, or any other advantageousgas or combination of gases known to skilled artisans. In oneembodiment, the housing is evacuated prior to sealing. In anotherembodiment, an electrical insulating liquid such as an oil or otherelectrically insulating liquids known to skilled artisans is containedwithin the housing.

In one embodiment, the implanted module contains an internal powersource, such as a battery. In another embodiment, the module is poweredtranscutaneously by induction of radio frequency current in an implantedwire coil connected directly to the module or connected by a flexiblelead containing electrical conductors, to charge an internal powerstorage device such as a capacitor.

In one embodiment, the pressure transducer is contained within ahermetically sealed sensor package, or module. The sensor package may beprovided in a wide range of sizes and shapes. In one embodiment, thesensor package is a cylindrical in shape with a distal end and aproximal end. In one embodiment, the module is between about 1 mm and 5mm long, and 3 mm in diameter. In another embodiment, the module isbetween about 5 mm and about 15 mm long. In another embodiment, thepackage is about 8 mm long, and about 3 mm in diameter. In oneembodiment, the package is less than about 1 mm in diameter. In anotherembodiment, the package is less than about 10 mm long. In oneembodiment, the package may be rectangular, square, spherical, oval,elliptical, or any other shape suitable for implantation. In oneembodiment, the sensor package is rigid, and in another embodiment, thesensor package is flexible.

In one embodiment, the sensor module includes a cylindrical housingcomprising one or more component pieces of titanium CP, titanium 6-4, orother suitable biocompatible metallic alloy or other material suitablefor making a hermetic package such as ceramic material like alumina orzirconia. Titanium pieces can be hermetically affixed to each other bylaser welding and ceramic materials may be hermetically bonded tometallic components by brazing techniques. In one embodiment, thehousing is closed at one end by a membrane called a diaphragm. In oneembodiment, comprising a titanium cylindrical housing, the diaphragmcomprises a titanium foil that is diffusion bonded or otherwisehermetically affixed to the titanium housing. In another embodiment, themembrane may be machined, lapped, or otherwise manufactured fromtitanium bar or rod stock so that part of the cylindrical housing andthe diaphragm are one piece. One skilled in the art will understand thatany construction techniques and material for creating a hermetic packagecan be used in accordance with several embodiments of the presentinvention. As used herein, the term hermetic shall be given its ordinarymeaning and shall also mean a device enclosure with a helium leak ratefrom about 1×10⁻¹¹ to about 5×10⁻¹³ std. cc/sec

In another embodiment, the pressure sensor is fabricated by microelectro-mechanical systems (MEMS) techniques, as taught by, for exampleU.S. Pat. No. 6,331,163, herein incorporated by reference. Electronicand mechanical devices are frequently placed in environments that maydamage the components unless some form of protection is provided. Forexample, some electronic medical devices implanted into a body may beexposed to body fluids that may cause unprotected semiconductor circuitsand non-electronic components to fail. Such devices may benefit from ahermetic packaging to limit exposure to these harmful elements.Traditional approaches to creating a protective hermetic package for animplantable medical device generally involve the complete encasement ofthe silicon or semiconductor components of the device in the hermeticpackage. Such packages typically utilize a metal such as titanium, or aceramic material like alumina or zirconia. Various glass materials havealso been employed. For example, hermetic cavities have been created toform small vacuum chambers for pressure transducers by bonding siliconcomponents to either silicon or glass. The silicon component is usuallyfixed into a package with epoxy or soldered into the package. Thecomplete encasement of the silicon component with a separate packageadds to the size of the device and also increases its cost.

Similarly, other approaches that have been used for pressure transducersby enclosing the sensor in a metal packaging and coupling theenvironmental pressure to the sensor through a diaphragm bonded to thepackaging. Such approaches place an interface between the environmentand the sensor for the electronic components to interact with theenvironment and to protect the integrity of the device. Such a diaphragmmay be made from the same or similar materials as the housing whichprotects the inner components to facilitate bonding and hermetic sealingof the diaphragm with the housing or protective barrier of the device.

In light of the above discussion, there still remains a need in the artfor a system to accommodate medical devices that function effectively byhaving direct contact of the silicon component with the environment (inmany cases, the body). The effective operation of some of these devicesprecludes complete encasement of the sensor in a protective package.Newer semiconductor components, however, such as semiconductor chemicalsensors, may require such direct contact of the silicon component,thereby precluding complete encasement of the sensor. Similarly,pressure sensors fabricated by micro electromechanical systems (MEMS)techniques, as described in U.S. Pat. No. 6,331,163, herein incorporatedby reference, require either direct contact with the environment oradequate transmission of environmental pressure through a medium to thesensor.

Accordingly, in one embodiment of the present invention, a method forhermetically sealing a silicon device is provided. The silicon device iscoupled to a sensor, such as a pressure transducer, which benefits fromhaving direct contact with its environment (the body). Thus, a method isprovided to hermetically seal the non-sensing portion of a silicondevice while allowing the sensing portion (e.g. the pressure transducer)to have direct contact with the body. In one embodiment, a silicon chip,a gold preform and a metallic housing are each primed for sealing andare assembled. The assembly is then heated to react the gold preform tothe silicon chip and to form a molten gold-silicon alloy in-situ to bindsaid metallic housing to the non-sensing portion of the silicon chip. Inthis way, the non-sensing portion of the silicon chip is hermeticallysealed, while still permitting exposure of the sensing portion of thesilicon chip to the environment.

In one embodiment, the physiological sensor system is configuredsimilarly to a cardiac pacemaker, with a hermetically sealed housingimplanted under the patient's skin (subcutaneous) and a flexible leadcontaining signal conductors with a hermetically sealed pressuretransducer module at or near its distal end. The signal conductors maybe electrical, fiber optic, or any other means of signal conductionknown to skilled artisans. The lead may have a stylet lumen to aid withtransducer deployment in the body of a medical patient. The lead mayhave a lumen for connection of the sensor module to a referencepressure. In one embodiment, the housing contains a battery,microprocessor and other electronic components, including transcutaneoustelemetry means for transmitting programming information into the deviceand for transmitting physiological data out to an externalprogrammer/interrogator. In another embodiment, the implanted pressuresensor lead combination is an integral part of a cardiac rhythmmanagement system such as a pacemaker or defibrillator or various otherimplantable cardiovascular therapeutic systems know to skilled artisans.

In another embodiment, the signal processing, and patient signalingcomponents are located in a device external to the patient's body incommunication with the implanted subcutaneous housing via one of variousforms of telemetry well known in the art, such as two-way radiofrequency telemetry. In this embodiment, the subcutaneous housing cancomprise only a tuned electrical coil antenna, or a coil antenna inconjunction with other components. Other designs for antennae are wellknown to those skilled in the art and are can be used in accordance withseveral embodiments of the present invention.

In still another embodiment, the sensor module is directly connected toa coil antenna by short lead or lead of zero length such that the entiresystem resides in the heart. Such a system may have a small internalbattery or power could be delivered transcutaneously by magneticinductance or electromagnetic radiation of a frequency suitable forpenetrating the body and inducing a voltage in the implanted coilantenna. In one embodiment, radiofrequency electromagnetic radiation isused with a frequency of about 125 MHz.

In one embodiment, the sensor module comprises one or more sensors inaddition to a pressure transducer at its distal end. These sensors mayinclude a plurality of pressure transducers to measure pressures in thetransmural space or locations proximal to the transmural space, or tomeasure differential pressure between the distal diaphragm and anotherlocation. Other types of sensors include, but are not limited to,accelerometers, temperature sensors, electrodes for measuring electricalactivity such as the intracardiac electrogram (IEGM), oxygen partialpressure or saturation, colorimetric sensors, chemical sensors forglucose or for sensing other biochemical species, pH sensors, and othersensor types that may be advantageous for diagnostic purposes, or forcontrolling therapy. Pressure sensors with a frequency response of fromabout 500 to about 2000 Hz are adequate to detect a wide range ofcardiac or respiratory sounds such as valvular closure, opening, murmursdue to turbulent blood flow, pulmonary rates due to congestion, etc. Afrequency response of less than about 500 Hz and greater than 2000 Hzcan also be used in accordance with several embodiments of the instantinvention. Alternatively, a separate hydrophone sensor may be placed inthe sensor module. In one embodiment, the sensor module may serve dualdiagnostic and therapeutic functions. In one embodiment, the sensormodule contains at least one electrode for stimulating the organ inwhich it is placed. For example, such an electrode or electrodes may beused for electrical pacing the left atrium. Other combinations withtherapeutic applications will be known to skilled artisans.

Left Atrial Pressure Signals

In one embodiment, one of the physiological sensors is a pressuretransducer that is used to generate a signal indicative of pressure inthe left atrial chamber of the patient's heart (the “left atrialpressure,” or LAP). In one embodiment, a LAP versus time signal isprocessed to obtain one or more medically useful parameters. Theseparameters include, but are not limited to, mean LAP, temporallyfiltered LAP (including low-pass, high-pass, or band-pass filtering),heart rate, respiratory variations of LAP, respiration rate, andparameters related to specific features of the LAP waveform such as theso-called a, v, and c waves, and the x, x′, and y descents. All theseparameters are well known to those skilled in the art. Examples ofparameters derived from specific LAP waveform features include themechanical A-V delay interval, as defined below (as distinct from theelectrical A-V interval derived from the electrocardiogram); therelative peak pressures of the a and v waves, and the pressure values atspecific times in the LAP waveform, as are understood by those skilledin the art.

In one embodiment, signals indicative of left atrial pressure areperiodic signals that repeat with a period the length of which is equalto the period in between heartbeats. Any portion of the signal or asummary statistic of that periodic signal may be indicative of leftatrial pressure and provide diagnostic information about the state ofthe heart. For example, the a, c, and v waves and the x, x′, and ydescents, described above, correlate with mechanical events such asheart valves closing and opening. Any one of these elements can yielduseful information about the heart's condition. Each discrete elementrepresents an individual signal indicative of left atrial pressure. Asummary statistic such as the arithmetic mean left atrial pressure alsorepresents a signal indicative of left atrial pressure. One skilled inthe art will appreciate that there are additional discrete elements andsummary statistics that are valuable indicators of left atrial pressure.Advantageously these components of left atrial pressure are relative toeach other and therefore do not have to be compensated for atmosphericpressure and are not subject to offset drift inherent in most pressuretransducers. Another such index will be the pressure differentialbetween the mean and respiratory minima.

In one embodiment, the relative heights and/or shapes of the left atrial“a,” “c,” and “v” waves are monitored to detect and diagnose changes inseverity of cardiovascular disease. This information permitsdifferentiation between worsening symptoms of CHF due to volume overloadversus impaired left ventricular pump function (such as decrease leftventricular compliance, or acute mitral regurgitation), allowing medicaltherapy to be appropriately targeted. For example, pure volume overloadis usually manifest with a progressive elevation of the mean left atrialpressure and generally responds to fluid removal by taking a diureticmedication, natriuretic peptide, or an invasive technique known asultrafiltration of the blood. Decreased left ventricular compliance isthe diagnosis when the “a” wave increases without shortening of theatrioventricular (AV) delay or in the presence of mitral stenosis.Acutely decreased compliance may be indicative of left ventricular (LV)ischemia, while chronically decreased compliance may be indicative of LVwall thickening know as hypertrophy. The former may respond to nitratesor coronary artery interventions, while the latter may respond to betaor calcium antagonist drugs, or chemical septal ablation. Increases inthe “v” wave amplitude and merging with the “c” wave to produce a “cv”wave is usually indicative of acute mitral valve regurgitation. This maybe due to a sudden mechanical failure of the valve or its supportingapparatus or it may be due to acute ischemia of the supporting papillarymuscles as part of an acute coronary artery syndrome. Sudden mechanicalfailure requires surgical repair or replacement, while ischemia mayrequire anti-ischemic medications such as nitroglycerin or coronaryartery interventions such as angioplasty or bypass surgery. In anotherembodiment, atrial fibrillation and atrial flutter are detected byanalysis of the LAP waveform. In another embodiment, spectral analysisof the LAP versus time signal is performed.

Measurement of Relative Pressure (Gauge Pressure)

In one embodiment, the system contains components to obtain a signalindicative of pressure relative to atmospheric pressure. An implantedapparatus for measuring absolute pressure at a location within the bodyis provided as above, which further communicates this information, aseither an analog or digital signal, to an external signalanalyzer/communications device. The external signalanalyzer/communications device further contains a second pressuretransducer configured to measure the atmospheric (barometric) pressure.The analyzer/communications device performs a calculation using theabsolute pressure from the implanted module and the atmospheric pressureto obtain the internal pressure relative to atmospheric pressure, thatis, difference between the absolute pressure at the location within thebody and the absolute barometric pressure outside the body. Thispressure, also known as the gauge pressure, is known to those skilled inthe art to be the most physiologically relevant pressure measure.

In one embodiment, gauge pressure measurements are performed only whenthe implanted apparatus is queried by the externalanalyzer/communications device, advantageously assuring that theatmospheric pressure at the time and patient's location is available andcorrectly matched with the absolute internal pressure reading. It willbe clear to those skilled in the art that unmatched internal andbarometric pressure readings would render the gauge pressure measurementinaccurate or useless. In this embodiment, internal absolutemeasurements are made only when the external analyzer/communicationsdevice is physically present. In one embodiment, this is accomplished byhaving the external device supply operating power to the implant moduleto make the measurement. In another embodiment, this is accomplished byrequiring a proximity RF link to be present between the external andimplantable modules, immediately before, after and/or during themeasurement.

In another embodiment, differential pressure is obtained by the leadcontaining a lumen that communicates a reference pressure to the sensormodule as well known to skilled artisans.

Anchoring/Fixation Apparatus

In several embodiments, the physiological sensor system is coupled tosurrounding tissue by one or more anchoring mechanism. In oneembodiment, tissue anchoring apparatus is used to affix the transducermodule in the desired transmural position, to prevent sensor modulemigration, to promote rapid tissue overgrowth without thrombusformation, and to be mechanically and biologically compatible with thetissue so as not to induce an inflammatory reaction or cause deviceerosion. In several embodiments, a pressure measurement device isanchored within an atrial septum wall. However, the skilled artisan willrecognize that the methods described for anchoring a pressure transducerto a septal wall can also be applied to affix any suitable sensingmodule to any wall of an organ or a vessel within a patient.

In one embodiment, the module is associated with proximal and distalanchoring systems that assure localized fixation of the distal end ofthe module and transducer diaphragm essentially coplanar with the planeof the blood contacting surface of the desired chamber or vessel so asto promote rapid tissue overgrowth. One such a system is described inU.S. patent application Ser. No. 10/672,443, herein incorporated byreference.

In one embodiment, an anchoring device is configured to cross the septumbetween the right and left atrium and trap itself between the twochambers such that a pressure-sensing member is exposed to the leftatrium. The device is configured in a manner that will allow positioningof the pressure-sensing member at a desired location relative to theseptal wall while conforming to anatomical variations. In oneembodiment, the diaphragm is essentially coplanar with the left atrialside of the intra-atrial septum. In one embodiment, the term“essentially coplanar” is defined as the plane defined by the outersurface of the diaphragm is within about ±0.5 mm distance of the planetangential to the left atrial side of the intra-atrial septum at thelocation it is traversed by the pressure-monitoring module. In anotherembodiment, this distance is defined as about ±1 mm. In yet anotherembodiment of the present invention, this distance is defined as about±2 mm.

In one embodiment, the device is designed such that the diaphragm willnot be recessed within the septal wall. This embodiment is particularlyadvantageous because thrombi are more likely to form in regions of bloodstasis within the recess. A thicker layer of neointima will tend to formas the tissue remodels, creating an optimal blood flow pattern byeliminating the recess. Likewise, a diaphragm that protrudes into theleft atrium may cause microscopic high shear zones where high velocityblood flow interacts with the device. High shear is known to activateplatelet thrombus formation. Also, the longer distance for tissuein-growth from the surrounding septum may delay tissue coverage andhealing. Nonetheless, one skilled in the art will understand that, inaccordance with a few embodiments of the current invention, a portion ofthe diaphragm may be recessed within the septal wall or may protrudethrough the left atrium.

According to one embodiment, the sensor system comprises a proximalanchor having one or more helical legs extending between a proximal ringand a distal ring. In one embodiment, the device also comprises a distalanchor having one or more legs. The device further includes ahermetically sealed pressure transducer module configured to besupported by the proximal and distal anchors. The proximal and distalanchors of this embodiment are preferably configured to be movablebetween a collapsed delivery position and an expanded position in whichthe proximal and distal anchors secure the module to a wall of an organwithin a patient.

In one embodiment of the current invention, a system for diagnosingand/or treating a medical condition in a patient using a device tomeasure pressure is provided. One embodiment comprises apressure-sensing module configured to be implanted within a patient, aproximal anchor comprising at least one helical leg configured to expandfrom a compressed state to a relaxed state, and a distal anchorcomprising at least one leg configured to expand from a compressed stateto an expanded state. The proximal anchor and the distal anchor of thisembodiment are preferably configured to sandwich an atrial septum wall(or the left atrial free wall, the pulmonary vein wall, or any othersuitable wall of a heart or a blood vessel) between the proximal anchorleg and the distal anchor leg and to support the module in the septumwall. In one embodiment, the system also comprises a delivery system,such as a catheter, configured to deploy the sensor, the proximalanchor, and the distal anchor in the septum wall. In one embodiment, thesystem is particularly suited to monitor congestive heart failure in thepatient.

Another embodiment provides a system for monitoring a patient forcongestive heart failure, comprising an implantable pressure transducerand a means for anchoring the pressure transducer to an organ wall. Inone embodiment, the means for anchoring comprises one or more anchoringmembers adapted to contact a proximal side and a distal side of a wallof an organ to anchor the pressure transducer to the organ wall. Thesystem can further comprise a means for delivering the implantabletransducer and means for contacting the organ wall.

In another embodiment, a method of monitoring congestive heart failurein a patient is provided. In one embodiment, the method comprisesproviding a pressure sensor secured to a proximal anchor and a distalanchor, and delivering the pressure sensor to a hole in an atrial septumof the patient's heart. The method further comprises deploying thepressure sensor with the proximal anchor on a proximal side of theseptum, and the distal anchor on a distal side of the septum; monitoringa fluid pressure in the left atrium of the patient's heart.

Another embodiment provides a method of monitoring congestive heartfailure within a patient. In one embodiment, the method comprisesproviding an implantable pressure transducer and coupling saidimplantable pressure transducer to a means for anchoring said pressuretransducer in an organ wall. The method further comprises deliveringsaid pressure transducer and said means for anchoring to said organwall, and causing said means for anchoring said pressure transducer insaid organ wall to expand, thereby capturing said organ wall andanchoring said pressure transducer thereto.

According to still another embodiment, a method of anchoring a device inthe heart of a patient is provided. The method includes providing animplantable cardiac anchoring device comprising a proximal anchor havingat least one helical leg and a distal anchor having at least one linearleg. The method comprises attaching an implantable pressure-sensingmodule to the implantable cardiac anchoring device, positioning atubular delivery catheter in a wall of a patient's heart, and insertingthe implantable module and the implantable cardiac anchoring device intothe tubular delivery catheter. The method further includes deploying thesensor and the implantable cardiac anchoring device such that the sensoris retained in a transverse orientation relative to the wall.

Turning to the figures, embodiments of cardiovascular anchoring devicesfor use in anchoring an implantable pressure sensor module to an organwall (such as an atrial septum wall) will now be described. In someembodiments, the module comprises a sensor, and in one particularembodiment, the module is a pressure sensor, such as a pressuretransducer. Several figures included herein illustrate a straight deviceand deployment apparatus for the purpose of demonstration. However, oneskilled in the art will understand that, in use, the delivery catheterand contained components will typically be substantially flexible or mayassume other non-straight shapes. For example, a delivery catheter canbe configured to include a pre-shaped curve or a pre-shaped stylet inorder to facilitate navigation of a patient's tortuous vasculature. Aswill also be clear to the skilled artisan, the flexibility of certaincomponents will be particularly advantageous for navigation throughtortuous anatomy.

FIG. 1 illustrates embodiments of an anchor and sensor assembly 100comprising a distal anchor 110 and a proximal anchor 112 configured tosecure a sensor 120 to a wall of an internal organ (such as a leftatrium of a heart) within a patient. The proximal and distal anchorcomponents 110 and 112 are configured to be compressed to a deliverystate such that they can be placed within a tubular delivery catheter.The anchors 110 and 112 are further configured such that when they arereleased from their compressed state, they will relax to assume apreformed, expanded configuration in which they engage opposite sides ofa septum wall 210 (e.g., see FIGS. 20 and 21) in order to support thesensor 120 in an operative position.

In order to allow the proximal and distal anchors 110 and 112 toself-expand from a compressed state to an expanded state, they arepreferably made from materials that exhibit superelastic and/or shapememory characteristics. Alternatively, the anchors could be made fromother non-superelastic or non-shape memory materials as desired. Forexample, suitable materials for fabrication of the proximal and distalanchors include, but are not limited to, nickel titanium alloys (NiTi orNITINOL), cobalt-chromium alloys, stainless steel, ELGILOY, MP35N orother biocompatible, superelastic, and/or shape memory materials thatare well known to those skilled in the art of clinical medical devices.The anchors can be made by any suitable process appropriate for aparticular material. For example, the anchors could be molded, machined,laser cut, etc as desired.

FIGS. 1 and 2 illustrate one embodiment of a distal anchor 110 in acompressed state and an expanded state respectively. The distal anchor110 generally comprises a cylindrical base portion 122 with a pluralityof legs 124 extending distally therefrom. In the illustrated embodiment,the legs 124 include slots 126 for the purpose to advantageously promotemore rapid tissue overgrowth in a deployed position, which willadvantageously aid in securement of the device to the septum wall andprevent thrombus formation. Referring to FIG. 26, any of a variety ofkeyed or slotted anchor configurations may be used. In anotherembodiment, the slots in legs 124 can vary in width. In anotherembodiment, the slots in legs 124 can be curved or serpentine. Inanother embodiment, the slots in legs 124 may be replaced by one or moreholes of equal or diverse diameters. In an alternative embodiment, thelegs 124 can be solid. In yet another embodiment, the legs 124 can bekeyed or slotted at right angles to their long axes from one or bothsides. Referring back to FIGS. 1 and 2, the distal anchor 112 alsocomprises struts or locking tabs 130 configured to engage a portion ofthe sensor 120 as will be further described below. In its compressedstate, as shown in FIG. 1, the distal anchor 124 occupies asubstantially cylindrical shape with its legs orient forward ordistally, thereby allowing it to be placed within a cylindrical, tubulardelivery catheter or delivery sheath. The forward orientation of thedistal anchors legs project distally beyond the pressure-sensingdiaphragm, and protect the diaphragm from being damaged during handlingor catheter passage into the body.

In an expanded shape, as shown in FIG. 2, the legs 124 of the distalanchor 110 bend outwards and proximally. In one embodiment, the legs 124bend outwards until they are substantially perpendicular to thelongitudinal axis of the cylindrical base portion 122. In alternativeembodiments, the legs bend proximally until they are oriented at morethan 90° to the longitudinal axis of the cylindrical base 122 as shownfor example in FIG. 8. In such embodiments, the angle θ (whichrepresents the amount beyond perpendicular to the longitudinal axis thatthe legs 124 can bend) can be between about 0° and about 20°. In someembodiments, the angle θ can be between about 5° and about 15°, and inone specific embodiment, the angle θ can be about 10°. In oneembodiment, the angle θ will preferably be reduced to zero degrees whenthe distal anchor 110 is deployed on a distal side of a septum wall 210(see FIG. 20) with a proximal anchor 112 on the proximal side of thewall 210 due to the opposing force of the proximal anchor 112. Thus, inone embodiment, the angle θ is selected along with a spring constant ofthe distal anchor legs 124 such that an opposing force applied by theproximal anchor 112 through a septum wall of a particular thickness (aswill be further described below) will cause the angle θ to besubstantially reduced to zero or to deflect a small amount in the distaldirection so as to conform with a substantially concave left atrialseptal surface. In doing so, wall contact is distributed over the entireproximal side surface area of the distal anchor legs to minimizepressure induced necrosis of the septum.

FIGS. 3-6 illustrate one embodiment of a proximal anchor 112 incompressed (FIG. 3) and expanded (FIGS. 4 through 6) states. In itscompressed state, the proximal anchor 112 occupies a substantiallycylindrical space such that it can be placed in a cylindrically tubulardelivery catheter. The proximal anchor 112 generally includes a proximalring 140 and a distal ring 142 with a plurality of legs 144 extendingtherebetween. The proximal anchor 112 can include any number of anchorlegs 144 as desired. For example, in the embodiment illustrated in FIG.3, the proximal anchor comprises six anchor legs 144. Alternatively, theproximal anchor 112 can include a greater or lesser number of anchorlegs 144. The proximal anchor 112 can also include struts or lockingtabs 150 which can be used to secure the sensor 120 to the proximalanchor as will be further described below.

In the embodiment of FIG. 3, the anchor legs 144 are configured tofollow a helical path between the proximal ring 140 and the distal ring142. In one embodiment, the helical path of the anchor legs 144 passesthrough 360 degrees between the proximal ring 140 and the distal ring142. In alternative embodiments, the proximal anchor 112 can be longerand/or the legs 144 can pass through 720 degrees. In general, it isdesirable that the legs pass through a substantially whole number ofcomplete circles between the proximal and distal rings 140, 142. Thisconfiguration allows the proximal anchor 112 to negotiate the tortuouspath that is typically encountered during delivery of the device to adesired location within a patient. The spiral or helical shape of theproximal anchor is particularly advantageous because this configurationequalizes bending stresses experienced by the anchor legs 144 in orderto maintain an internal lumen (typically with a circular cross-section)of the proximal anchor 112 as the device is navigated through a tortuouspath. Additionally, the illustrated configuration advantageouslyincreases flexibility of the proximal anchor 112 and reduces itsdiameter to allow the anchor to be more effectively negotiated through atortuous anatomy without damaging the device or injuring the patient.

FIGS. 4-6 illustrate the proximal anchor 112 in its expanded state. Asshown, proximal anchor 112 preferably assumes a substantially“mushroomed” shape in its expanded state. In moving between thecompressed and expanded states (assuming the distal ring 142 is heldsubstantially stationary), the anchor legs 144 preferably unwind andbuckle outwards and distally relative to the proximal ring 142. Asshown, the proximal anchor 112 preferably “unwinds” such that theproximal ring 140 rotates relative to the distal ring 142 as the anchor112 moves between its compressed and expanded states. The amount ofrotation of the proximal ring relative to the distal ring will typicallybe a function of the final resting distance between the proximal ringand the distal ring.

In their fully expanded state, the anchor legs 144 preferably bendoutwards and distally until each leg 144 forms a loop 152 with a distalmost edge 154 that is positioned substantially distally from the distaledge of the distal ring 142. In some embodiments, the anchor assemblycan be configured such that, in free space (i.e. with no tissue ormaterial between the proximal and distal anchors), the distal edge 154of the proximal anchor leg loops 152 and the proximal tissue-contactingsurface of the distal anchor 110 can actually overlap by up to about0.06″. In some embodiments the overlap can be between about 0.03″ andabout 0.05″, and in one embodiment, the distance is about 0.04″. In somenon-overlapping embodiments (as shown in FIG. 5), the distance 156between the distal edge 154 of the proximal anchor leg loops 152 and thedistal edge of the distal ring 142 of the proximal anchor can be betweenabout 0.040″ and about 0.070″. In some embodiments, the distance 156 isbetween about 0.050″ and about 0.060″, and in one particular embodiment,the distance 156 is about 0.054″. By providing the proximal and distalanchor legs 144 and 124 with sufficient resilience that they relax tooverlapping positions, it can be assured that the assembly will be ableto securely anchor to even the thinnest of septum walls. By selectingcertain mechanical properties of the proximal anchor, its elasticity canbe matched to that of the tissue wall it is to contact, thus minimizingthe chances for pressure induced tissue necrosis and subsequent erosionof the device through the septum.

FIGS. 7-9 illustrate the distal anchor 110 mounted to a sensor module120. In the illustrated embodiment, the sensor 120 is a pressuretransducer having a substantially cylindrical body 160 with apressure-sensing face 162 at its distal end, and a lead-attachmentinterface 164 at its proximal end. In one embodiment, as shown, thelead-attachment interface comprises a series of annular notches whichcan be engaged by a tightly-wound coil to secure the electrical lead. Insome embodiments, a lead-attachment mechanism can be welded in place(such as by laser welding) on the sensor 120 in order to provide a moresecure connection. In another embodiment, the lead-attachment interface164 can comprise screw threads. Alternatively, the skilled artisan willrecognize that any number of suitable alternative interfaces could alsobe used. Additional details of a suitable pressure sensor are provided,for example, in U.S. Pat. No. 6,328,699 to Eigler et al., which isincorporated herein by reference. In alternative embodiments, the sensor120 can be configured to sense and/or monitor any desired parameterwithin a patient.

In the embodiment of FIGS. 7-9, the distal anchor 110 is secured to thesensor 120 by struts or locking tabs 130 on the anchor, which engage anangled annular groove 170 which circumscribes a distal portion of thesensor 120. The locking tabs 130 extending distally from the distalanchor 110 (as shown in FIGS. 1 and 2) are preferably bent slightlyradially inwards such that they will engage the distal annular groove170 in the sensor as shown in the detail view of FIG. 9. Similarly, aproximal annular groove 172 is provided to be engaged by the lockingtabs 150 of the proximal anchor 112 (shown in FIG. 3). Theanchor-to-sensor attachment system illustrated in FIGS. 7-9 allows theanchors 110 and 112 to rotate about the sensor 120. In some situationsit is desirable to prevent rotation of the anchors relative to thesensor 120 by spot-welding the proximal and/or distal anchors to anannular flange 174 provided on the sensor 120. Alternatively, in placeof an annular groove, the sensor could comprise angled notches forreceiving the locking tabs in a single rotational orientation on thesensor 120. Alternatively still, other attachment systems can also beused, such as welds, adhesives, and other mechanical fasteners.

FIG. 8 illustrates a cross-sectional view of the sensor 120 attached toa distal anchor. In some embodiments, it may be desirable to vary thedistance 166 between a distal most edge of a distal anchor leg 124 (inan expanded state as shown) and the pressure-sensing face 162 of thesensor 120. In one embodiment, the distance 166 is preferably zero,i.e., the pressure-sensing face 162 is preferably substantiallyco-planar with the distal most point of a deployed distal anchor leg124. Such a configuration will preferably advantageously place thepressure-sensing face 162 substantially flush with the atrium wall,thereby reducing the hemodynamic effect experienced by the sensor 120,minimizing the effect of the sensor 120 on blood flow patterns, thusreducing the initiation of thrombus formation, and minimizing the pathlengths for tissue to overgrow the sensor diaphragm. In alternativeembodiments, it may be desirable that the sensor 120 be moved distallysuch that the pressure-sensing face extends distally outwards from thedistal anchor. Alternatively still, it may be desirable to support thesensor 120 within the distal anchor 110 such that the sensor face 162 isrecessed within the distal anchor 110. The location of the sensor facerelative to the distal anchor can be varied by changing a location ofthe distal annular groove 170 and/or by varying a size of the lockingtabs 130.

FIGS. 10-14 illustrate an alternative embodiment of an anchor and sensorassembly 100 wherein the components are attached to one another withinterlocking mechanical fasteners. As shown, the proximal anchor 112,the distal anchor 110, and the sensor 120 include interlockingstructures configured to mechanically interconnect the assemblycomponents in such a way as to limit both axial and rotational movementof the components relative to one another.

The distal anchor of FIGS. 10-12 comprises a plurality of fingers 180which extend proximally from the cylindrical base portion 122. As shown,each finger 180 can include a narrow neck section 182 and a widerproximal tab section 184. The proximal anchors 112 can includecorrespondingly shaped slots 186 in the distal ring 142 to receive thefingers 180. The sensor 120 can also include corresponding interlockingstructures configured to engage structures on the distal and/or proximalanchors 110, 112. As shown the sensor 120 can include raised sections188 around the circumference of the cylindrical body 160. The raisedsections 188 can be positioned so as to leave gaps 190 for receiving theneck sections 182 of the fingers 180. The raised sections 188 can bemachined into the cylindrical body 160 of the sensor, or they cancomprise independent segments welded, adhered, or otherwise secured tothe cylindrical body 160 of the sensor 120. The components can beassembled as shown in FIG. 10 to provide a secure and substantiallyimmobile connection between the proximal anchor 112, the sensor 120 andthe distal anchor 110. The specific geometry of the interlockingstructures of FIGS. 10-12 are intended to be merely exemplary, and thespecific shapes of the fingers 180, slots 186, and spaces 190 canalternatively include a variety of different geometric shapes in orderto provide a secure connection between the components. If desired, theinterlocking structures can also be welded together once they areassembled, thereby further securing the connection.

Radiopaque Markers

In one embodiment, one or more radiopaque markers are used inconjunction with deployment of the physiological sensor. FIGS. 13 and 14illustrate the proximal and distal anchors of FIGS. 10-12 with theaddition of a plurality of radiopaque markers 200 for facilitatingvisualization of the assembly under fluoroscopy during deployment. Asshown, radiopaque markers 200 can be applied to the legs 124 of thedistal anchor 110 and/or to the proximal ring 140 of the proximal anchor112. Radiopaque markers can also be provided on other portions of theproximal anchor 112, the distal anchor 110 and/or the sensor 120. Theradiopaque markers are preferably placed in “low flex zones,” such asthe tips of the distal anchor legs 124 and the proximal ring 140 of theproximal anchor. Generally, “low flex zones” are portions of the anchorthat experience substantially minimal flexing or bending. One advantageof this embodiment is that the materials used in the radiopaque markerswill not negatively affect the elasticity of the flexing anchorsections. Another advantage is that the radiopaque markers will notseparate from the anchor within a patient.

Radiopaque markers are typically made of noble metals, such as gold,platinum/iridium, tantalum, etc, and are typically attached to theanchor by selective plating or ion beam deposition. Alternatively, themarkers could be micro rivets and/or rings that are mechanicallyattached to portions of the system components. In order to reduce therisk of galvanic corrosion which can be experienced by dissimilar metalsexposed to blood, the radiopaque material can be selected to have agalvanic corrosion potential that is substantially similar to a galvaniccorrosion potential of the material from which the anchors and/or sensorare made. For example, if the anchors 110, 112 are to be made ofNITINOL, the radiopaque markers 200 can be made of tantalum.Alternatively, an electrically insulating coating (conformal coatings)such as parylene or other biocompatible synthetic material can be usedto cover the radiopaque markers in order to isolate the marker andanchor section from exposure to the blood or other bodily fluid.

In one embodiment, the legs 144 of the proximal anchor 112 apply a lowerspring force to the septum wall 210 than the legs 124 of the distalanchor 110 so that variations in septum wall thickness are accommodatedby variations in the position of the proximal anchor legs 144 as shownin FIGS. 20 and 21. FIG. 20 shows a relatively thin septum wall 210 witha thickness 230. In order to securely anchor the sensor, the legs 144 ofthe proximal anchor 112 will extend distally until their distal motionis stopped by the pressure of the septum wall 210. In the embodiment ofFIG. 21, the septum wall 210 is substantially thicker 231, therebycausing the legs 144 of the proximal anchor 112 to extend a shorterdistance distally than in the embodiment of FIG. 20.

FIGS. 27A-C, 28 and 29A-B show another embodiment of the proximalanchoring assembly. In this embodiment, the legs 320 of the proximalanchor 322 attach in a similar manner to the embodiment shown in FIGS.10-12, but the outer ends 324 of the anchor legs are left free. The legsare pre-formed into a predetermined shape such that when a deliverysheath 326 is withdrawn the legs 320 return to the desired deployedshape. In this embodiment, the proximal anchors are configured to foldforward (distally) upon retraction of the system into the deliverysheath, advantageously allowing the device to be retrieved and possiblyre-deployed if necessary.

FIGS. 30 and 31 show two embodiments of the present invention. Thesystem shown in FIG. 30 is configured with a proximal anchor havinghelical legs 144 and with the diaphragm 302 essentially coplanar withthe distal anchor legs 124. FIG. 31 shows another embodiment of thepresent invention, comprising small, barb-like, proximal anchors 145 andconfigured with the sensor diaphragm 302 protruding distally from theplane of the distal anchor legs 124. The neointima depicted in FIG. 31is not as thick as in Figure NF30 because in some embodiments, the smallbarb-like proximal anchors 145 may reduce chronic irritation compared tothe larger, spring-loaded helical proximal anchors 144. The tissuethickness overlying the sensor diaphragm 302 is further reduced in theconfiguration of FIG. 31 due to the protrusion of the diaphragm 302 awayfrom the septal wall.

Diaphragm Mechanics and Material Properties

In one embodiment, the transducer module distal diaphragm is arelatively thick titanium membrane such that its compliance (defined asthe change in displacement of the center portion of the diaphragm perchange in unit pressure) is substantially lower than the compliance ofthe overlying tissue encapsulation thus assuring that the motion of thediaphragm in response to changes in fluid pressure is only minimallyreduced by tissue overgrowth. In one embodiment, a 2.5 mm diameterdiaphragm is between about 0.001 to 0.003 inches (25 to 76 microns)thick. In another embodiment, the diaphragm thickness is between about0.003 to 0.005 inches (76 to 127 microns). Diaphragms of this type haverelatively low compliance, meaning that they exhibit relatively littlestrain, or displacement, in response to changes in pressure. Forexample, in one embodiment, a 2.5 mm diameter by 50-micron thicktitanium foil diaphragm has a displacement at its center of only about 4nm per mm Hg pressure change. One advantage of using a low compliancediaphragm is that tissue overgrowth will minimally affect the relativelyreduced range of motion, thus minimizing errors in the sensed pressurereading. Generally, the more non-compliant a diaphragm is, the moresensitive or higher gain the internal transducer components may need tobe to maintain the output signal amplitude.

In general, the motion of the center of the diaphragm, assuming uniformdiaphragm thickness, small deflections, infinitely rigid clamping aroundthe diaphragm periphery, perfectly elastic behavior and negligiblestiffening and mass effects due to presence of strain gauges on thediaphragm, is given by the equation$Y_{c} = \frac{3{{PR}_{o}^{4}( {1 - v^{2}} )}}{16t^{3}E}$

-   -   where: Y_(c)=center deflection (mm), P=pressure (Pa),        R_(o)=diaphragm radius (mm), v=Poisson's ratio (dimensionless),        t=diaphragm thickness (mm), and E=modulus of elasticity (Pa).

In one embodiment, the pressure transducer diaphragm is constructed ofTi 6-4 with material properties comprising of approximately R_(o)=1.1mm, v=0.31, t=0.05 mm, and E=100 GPa. Such a titanium diaphragm willhave very small deflections, about 2.4×10⁻⁶ mm/mm Hg. Tissue growth oversuch a diaphragm can be modeled by the material properties of the aortawhere v=0.30, t=0.5 mm (10 times the diaphragm thickness), and E=1 MPaor 100,000 times more elasticity than titanium. Such tissue will bedisplaced approximated 2.6×10⁴ mm/mm Hg, or about 100 times more thanthe titanium diaphragm. Thus, such tissue overgrowth will inhibit themotion of the titanium diaphragm by less than about 1.0%, thus having aclinically negligible effect on sensor gain over the range ofphysiologic pressures expected in the left atrium. Halving the diaphragmthickness to about 0.025 would cause similar tissue overgrowth toinhibit the motion of the diaphragm by more than about 7% and, if otheradjustments are not made, may cause clinically significant errors overthe physiologic range of expected left atrial pressures.

In one embodiment, the pressure transducer membrane is designed to havevery low compliance. In one embodiment, a low compliance pressuretransducer is fabricated using titanium foil as described above. Inanother embodiment, a low compliance pressure transducer is fabricatedfrom, for example, silicon, using micro electromechanical systems (MEMS)techniques.

While the effect of tissue overgrowth on sensor gain may be minimized byaspects of this invention described above, the skilled artisan willrecognize that any force on the sensor produced by contact with tissuewill cause a positive offset in the sensed pressure. If suchtissue-contact force is constant, then it will be clear to one skilledin the art that the offset produced thereby may be simply subtractedonce its magnitude is determined by comparison of the measured pressurewith a known pressure. However, if the tissue-contact force is notconstant, a time-varying pressure waveform artifact will be produced.Such may be the case if changes in the stretch or wall tension of theintra-atrial septum produce changes in tissue-contact force on thediaphragm. In embodiment of the invention, the sensor assembly isdesigned to decouple intra-atrial stretching or tension from the tissuein contact with the diaphragm. As shown in FIG. 32, in one embodiment adistal rim or ring 301 is provided surrounding the sensor diaphragm 302,such that the stretching is opposed by the ring rather than being forcedagainst the diaphragm 302. The ring 301 serves to isolate the tissueover the diaphragm 302 within it, so that tension within the surroundingtissue is not transmitted to the diaphragm 302. FIGS. 33 to 35 showadditional embodiments designed to decouple the diaphragm 302 fromsurrounding tissue. In FIG. 33 drug delivery is provided on adrug-eluting structure or band 303 about the sensor housing. It will befamiliar to those skilled in the art that antiproliferative drugs suchas paclitaxel or sirolimus have been used successfully to reduceneointimal proliferation within intravascular stents. In one embodimentof the present invention, a band 303 of drug is provided to limit theingrowth of tissue over the sensor diaphragm. The skilled artisan willrecognize that in some embodiments, a thin neointimal covering isadvantageous for reducing the risk of thrombosis. Therefore, in oneembodiment, channels 305 free of antiproliferative drug are providedacross the drug band 303 to allow for a thin layer of neointima to formover the portion of the sensor that protrudes into the blood within theleft atrium.

FIG. 34 shows an embodiment of the present invention comprisingcircumferential grooves 620 to which ingrowing tissue will adhere,providing mechanical isolation of the diaphragm 302 from the surroundingtissue. FIG. 35 shows another embodiment, where protruding tabs 622 areprovided to which ingrowing tissue may adhere, providing mechanicalisolation of the diaphragm 302.

Implantation Apparatus and Techniques

Many of the embodiments of implantable devices shown and describedherein are preferably configured to be deployed via a tubular, flexibledelivery catheter that can be guided either alone or over a guidewire toa delivery location within a patient. A delivery catheter for use indelivering and deploying an implantable device preferably comprises aninternal diameter that is at least as large as the outer diameter of thedistal and proximal anchors in their compressed states. In someembodiments, a delivery catheter can be configured to be sufficientlylarge in diameter to allow the catheter to be filled with a continuouscylindrical column of fluid surrounding the sensor module and its lead.This advantageously allows for simultaneous monitoring of a fluidpressure at the distal end of the catheter through the continuous fluidcolumn surrounding the anchoring system in the catheter. Such anarrangement would also advantageously allow for the injection of aradiographic contrast medium through the delivery catheter in order todetermine the precise location of the catheter tip in the cardiovascularsystem. The proximal portion of the catheter may contain a hemostaticadaptor to prevent back bleeding through the catheter around thepressure transducer system and to prevent the entrainment of air duringtransducer insertion and advancement. The skilled artisan will recognizethat other embodiments of delivery catheters incorporating additionalfluid-carrying lumens can also be used to deliver an implantableanchoring device. FIGS. 15-21 illustrate several embodiments of systemsand methods for delivering and deploying the anchor assembly 100 tosecure a sensor 120 in a septum wall 210. According to one embodiment, atraditional transseptal catheterization is performed using theBrockenbrough needle/catheter system. Thereafter a guidewire is placedthrough the septum wall 210 at the target site. A dilator/hemostaticdelivery catheter combination can then be fed over the guidewire andinto the left atrium. The guidewire and dilator can then be removed, andthe distal tip of the hemostatic delivery catheter crosses the septumand remains in the left atrium. Positioning can be determined underfluoroscopy by contrast injection and pressure measurement thought sidearm port the delivery catheter.

As shown in FIGS. 15 and 16, an assembly 100 of a proximal anchor 112, adistal anchor 110 and a sensor 120 is provided within an introducersheath configured to introduce the anchor assembly into the proximal endof the delivery catheter 220. In one embodiment, the introducer sheathis made of transparent tubing, such as acrylic, advantageously allowingthe operator to verify that all air bubbles have been flushed from theintroducer sheath before it is inserted through the hemostatic adaptorof the delivery catheter. A stylet 224 is advanced through a centrallumen of the electrical lead 226 to provide column strength and guidanceto the device.

The introducer sheath containing the anchor and sensor assembly is theninserted into the proximal end of the delivery catheter, and theintroducer sheath is retracted and withdrawn. The anchor assembly isthen guided through the delivery catheter 220 (which was previouslypositioned through the septum wall) until the legs of the distal anchor110 are positioned at the distal end of the delivery catheter 220, whichcan be visually verified under fluoroscopy by noting the alignment ofthe distal radiopaque marker 225 on the distal edge of the deliverycatheter 220 with the distal end of the sensor assembly 100. Thedelivery catheter 220 can be withdrawn while holding the anchor andsensor assembly 100 in place with the stylet 224 that extends throughthe center of the sensor lead 226. The stylet 224 is preferablyconfigured to provide sufficient column strength to allow the anchor andsensor assembly 100 to be held in place relative to the septum 210 whilethe catheter 220 is retracted to expose and deploy the distal anchorlegs 124, as shown in FIG. 17. Alternatively, the catheter 220 can beheld in place and the stylet 224 and sensor assembly 100 can be advancedto deploy the distal anchor legs 124.

In one embodiment, after the distal anchor legs 124 expand to assumetheir expanded state on a distal side of the septum wall 210, contrastmaterial is injected to assure correct positioning in the left atrium.The catheter 220 is further retracted while holding the stylet 224 andsensor assembly 100 in place until the distal edge of the catheter 220is coincident with the proximal end of the sensor assemble 100. Furthercontrast is injected while the entire catheter 220, stylet 224 andsensor assembly 100 are retracted in 1 to 2 mm increments until contrastmaterial exiting the tip of the catheter 220 is observed on fluoroscopyto exit into the right atrium. At this point further retraction of thecatheter 220 will expose the proximal anchor 112, allowing it to relaxto its expanded state on a proximal side of the septum wall 210 as shownin FIGS. 18 and 19. The fully deployed proximal 112 and distal 110anchors preferably resiliently engage the septum wall 210 in order tofirmly secure the sensor 120 to the septum wall 210.

In one embodiment, to facilitate tissue overgrowth, the path lengths fortissue to in-grow over the distal anchor fixated to the left atrial sideof the septum is minimized by creating one or more perforations, holes,pores, or slots in the distal anchor legs 124. For example, FIGS. 1, 2and 7 show slots 126 in the legs 124 of the distal anchor 110. In oneembodiment, surface grooves or channels are used in at least a portionof the device to facilitate tissue growth. In another embodiment, shownin FIG. 26, at least one groove is placed on the diaphragm surface or onthe anchor legs to serve a similar purpose. The groove's long axes canbe linear, circumferential, and serpentine or any other beneficial shapeand the groove's cross section can be rectangular, semi-round, or anyother beneficial shape.

Exemplary modes of operation for one embodiment of the invention aredescribed as follows. The following Example illustrates variousembodiments of the present invention and is not intended in any way tolimit the invention.

EXAMPLE 1

In Vivo Studies

Several of the discoveries in this patent application results from theinventor's first hand experience percutaneously implanting transmuralpressure transducer and anchor systems with catheter delivery systemssimilar to those depicted in FIGS. 1 through 21, in the left atrium of 3anesthetized pigs. In these experiments, a transseptal catheterizationwas performed from the right internal jugular vein placing the distaltip of an 11 French×25 cm long, peel-away, hemostatic valve, side-armdelivery catheter in the left atrium under fluoroscopic guidance(Pressure Products). The pressure transducer systems were delivered tothe desired location traversing the septum each time. Pigs were observedwith transducer system in situ for 0 days, 3 weeks, and 18 weeks andperiodic ambulatory pressure readings were obtained using aradiofrequency telemetry system coupled to a palm type computer. Thepigs survived for 3 and 18 weeks were returned to the catheterizationlaboratory at the time of euthanasia for repeat catheterization with afluid filled catheter to validate pressure readings from the implants.After euthanasia, the hearts were opened and photographs of the grossspecimens obtains. The hearts with the pressure transducer and anchoringsystem in place were fixed in formalin for more 72 hours. Thesespecimens with transducers in situ were placed in a controlled pressurechamber and calibration functions obtained. After calibration,microscopic sections stained with hematoxylin and eosin, and trichromestains were reviewed by an expert cardiovascular pathologist

After opening the left atrial free wall in the pig sacrificedimmediately after implantation it was observed that the diaphragm wascoplanar, protruding less than 0.5 mm from the surrounding left atrialsurface. The distal anchor was flat against the left side of the septumand the proximal anchor was contacting the right side of the septum.Perturbation of the system along any axis was counterbalanced such thatwhen the perturbation force was relieved, the transducer/anchor systemrestored itself to the original coplanar position.

For the pig euthanized 3 weeks after transducer deployment, thediaphragm and all 3 legs of the distal anchor were again ideallyoriented coplanar with the left atrial wall. It was noted that thelocation of transmural puncture was somewhat posterior of the thinnestportion and probably made from a non-orthogonal approach. Nevertheless,the device was orthogonally oriented related to its internal restorativeforce configuration. On the left atrial side of the septum, thetransducer diaphragm and the distal anchor legs were entirely coveredwith a thin, translucent layer of neoendocardium. Histologic sectionsreveal that the covering tissue was comprised of normal granulationtissue, morphologic smooth muscle cells and fibrocytes without a chronicinflammatory reaction. We obtained ambulatory recordings of the leftatrial pressure repeatedly during the 3 week survival. After sacrifice,with the transducer in situ covered with tissue, repeat calibrationshowed that in comparison to the pre-implantation calibration, there wasno change in gain and small change in offset of less than about 2 mm Hg

For the pig euthanized 18 weeks after transducer deployment it was notedagain that the location of transmural puncture was somewhat posterior ofthe thinnest portion and probably made from a non-orthogonal approach.Once again, the device was correctly oriented related to its internalrestorative force configuration. On the left atrial side of the septum,the transducer diaphragm and the distal anchor legs were now entirelycovered with a much thicker, opaque layer of neoendocardium. Histologicsections reveal that the covering tissue was comprised of fibrous tissuestaining positively for collagen and there was no inflammatory reaction.We obtained ambulatory recordings of the left atrial pressure repeatedlyduring the 18 week survival. As shown in FIG. 25, after euthanasia, withthe transducer in situ covered with tissue, repeat calibration showedthat in comparison to the pre-implantation calibration, there was a 0.5%reduction in gain and a clinically insignificant change in offset ofless than about 3 mm Hg

The apparatus and methods of several embodiments of the presentinvention may be embodied in other specific forms and for otherapplications without departing from its spirit or essentialcharacteristics. The described embodiments are to be considered in allrespects only as illustrative and not restrictive.

Although certain embodiments and examples have been described herein, itwill be understood by those skilled in the art that many aspects of themethods and devices shown and described in the present disclosure may bedifferently combined and/or modified to form still further embodiments.Additionally, it will be recognized that the methods described hereinmay be practiced using any device suitable for performing the recitedsteps. Such alternative embodiments and/or uses of the methods anddevices described above and obvious modifications and equivalentsthereof are intended to be within the scope of the present disclosure.Thus, it is intended that the scope of the present invention should notbe limited by the particular embodiments described above, but should bedetermined only by a fair reading of the claims that follow.

Additionally, the skilled artisan will recognize that the embodiments ofanchoring devices and methods described herein may be advantageouslyapplied for implanted pressure transducers transmurally positioned on,in or through a wall of any organ or vessel within a patient. It willalso be apparent to one skilled in the art that the field of use of theembodiments of devices and methods described herein extends beyond thespecific condition of heart failure to any cardiovascular condition orother condition in a medical patient where a device is implanted througha wall of a chamber or vessel or is affixed to a wall of that chamber ofvessel.

1. An implantable pressure sensing system, comprising: a pressure sensorassembly, said pressure sensor assembly comprising: a sensing interfacehaving a first face and a second face; and at least one pressure sensingunit comprising a sensing surface and non-sensing surface, wherein saidpressure sensing unit contacts said second face of said sensinginterface; and a sensor housing, wherein said sensor housing ishermetically sealed to said pressure sensor assembly; wherein at leastportion of said sensing interface is adapted to reduce thrombosis. 2.The implantable pressure sensing system of claim 1, wherein said sensinginterface of the pressure sensor assembly comprises a diaphragm.
 3. Theimplantable pressure sensing system of claim 1, wherein at least onesaid pressure sensing unit comprises a strain gauge.
 4. The implantablepressure sensing system of claim 1, wherein said sensing interface andsaid pressure sensing unit are integrally formed in a microelectromechanical systems device.
 5. The implantable pressure sensingsystem of claim 2, wherein at least a portion of said diaphragmcomprises a plurality of grooves to facilitate tissue ingrowth.
 6. Theimplantable pressure sensing system of claim 2, wherein at least aportion of said diaphragm has a biocompatible coating.
 7. Theimplantable pressure sensing system of claim 6, wherein saidbiocompatible coating is bio-stable.
 8. The implantable pressure sensingsystem of claim 6, wherein said biocompatible coating is bio-erodable.9. The implantable pressure sensing system of claim 6, wherein saidbiocompatible coating is resistant to thrombus formation.
 10. Theimplantable pressure sensing system of claim 6, wherein saidbiocompatible coating is capable of controlling tissue ingrowth.
 11. Thesystem of claim 6, wherein said biocompatible coating is configured toreduce formation of fibrous tissue.
 12. The implantable pressure sensingsystem of claim 11, wherein said biocompatible coating does not reducegrowth of endothelial tissue.
 13. The implantable pressure sensingsystem of claim 1, wherein at least a portion of said sensor housing isconfigured to resist transmission of side-load forces to said sensinginterface under physiologic conditions.
 14. The implantable pressuresensing system of claim 13, wherein said sensor housing comprises aside-loading force absorbing structure about the sensing interface. 15.The implantable pressure sensing system of claim 1, wherein at least aportion of said sensor housing has a polished surface.
 16. Theimplantable pressure sensing system of claim 1, wherein at least aportion of said sensor housing has a thrombosis-resistant coating. 17.The implantable pressure sensing system of claim 1, wherein said sensorhousing comprises one or more materials selected from the groupconsisting of nitinol, stainless steel alloys, titanium alloys, cobaltchromium, tantalum, a ceramic, a glass or combination thereof.
 18. Theimplantable pressure sensing system of claim 1, further comprising adrug-eluting component.
 19. The implantable pressure sensing system ofclaim 18, wherein said drug-eluting component comprises a plurality ofreservoirs on the surface of said sensor housing with depots of one ormore releasable treatment agents.
 20. The implantable pressure sensingsystem of claim 20, wherein said drug-eluting component furthercomprises a drug for controlling neointimal thickness.
 21. Theimplantable pressure sensing system of claim 2, wherein said diaphragmis configured to resist the inhibition of diaphragm motion by overlyingtissue overgrowth.
 22. The implantable pressure sensing system of claim21, wherein said diaphragm has a compliance substantially lower than thecompliance of physiological levels of overlying tissue overgrowth. 23.The implantable pressure sensing system of claim 22, wherein saiddiaphragm has an average thickness sufficient to provide a compliancesubstantially lower than the compliance of physiological levels ofoverlying tissue overgrowth while capable of a displacement sufficientfor said strain gauges to generate a usable sensor signal over aphysiological range of blood pressures.
 24. The system of claim 23,wherein said diaphragm has a diameter of about 2.5 mm and an averagethickness of about 25 microns to about 76 microns.
 25. The implantablepressure sensing system of claim 23, wherein said diaphragm has adiameter of about 2.5 mm and an average thickness of about 76 microns toabout 127 microns.
 26. The implantable pressure sensing system of claim24, wherein said diaphragm has a diameter of about 2.5 mm, an averagethickness of about 50 microns, and a displacement of about 4 nm at aboutthe center of said diaphragm.
 27. The implantable pressure sensingsystem of claim 22, wherein said diaphragm has a compliance of about10,000 times less or lower than the compliance of physiological levelsof overlying tissue overgrowth.
 28. The implantable pressure sensingsystem of claim 27, wherein said diaphragm has a compliance of about100,000 times less or lower than the compliance of physiological levelsof overlying tissue overgrowth.
 29. The implantable pressure sensingsystem of claim 23, wherein said first face and said second face of saiddiaphragm are generally flat to enhance diaphragm displacementcapability.
 30. The implantable pressure sensing system of claim 21,wherein said diaphragm comprises a material selected from a groupconsisting of titanium or Ti 4-6.
 31. The implantable pressure sensingsystem of claim 1, wherein the sensor housing further comprising afilling material within the sensor housing.
 32. The implantable pressuresensing system of claim 31, wherein the filling material is selectedfrom one or more of the group comprising helium, argon or other noblegas, an electrical insulating liquid, or a moisture absorbent material.33. An implantable pressure sensing system, comprising: a pressuretransducer assembly comprising a micro electromechanical systemspressure transducer; said pressure transducer having a first face with asensing surface and a non-sensing surface, and a second face having aconnection area and a non-connection area; a sensor housing, whereinsaid sensor housing is hermetically sealed to said pressure transducerassembly; wherein said sensing surface of the pressure transducer isconfigured to reduce thrombosis.
 34. The implantable pressure sensingsystem of claim 33, wherein said sensor housing is hermetically sealedto said pressure transducer assembly at the non-sensing surface of saidfirst face.
 35. The implantable pressure sensing system of claim 33,wherein said sensor housing is hermetically sealed to said pressuretransducer assembly at the non-connection area of said second face. 36.The implantable pressure sensing system of claim 33, wherein said sensorhousing is hermetically sealed to said pressure transducer assembly witha gold-silicon bonding layer.
 37. A device for monitoring a patient,comprising: a means for sensing a physiological parameter; animplantable means for housing the sensing means; a means for interfacingthe sensing means with the patient environment; and a means for reducingthrombosis on the interfacing means.